Pharmacokinetics
The research topic in the pharmacokinetics studies is the development of new drugs or pharmaceutical formulations, which allow to guarantee the blood drug concentration in the therapeutic window for as long as possible. The therapeutic window is represented by the concentration range between a minimum value, known as ‘minimum effective concentration’ (below this value the drug is clinically inefficient), and a maximum value, known as ‘minimum toxic concentration’ (above this value the drug toxic effects appear). The pharmacokinetics deals with the interaction between the molecules and the body, studying the effects that the body causes on the drug, including: absorption, distribution, metabolism, and elimination. These processes are known with the acronym ‘ADME’.
Every year, the pharmaceutical industries use several hundred lab animals to study drugs pharmacokinetics. It has to be highlighted that the basic principle in the scientific studies is that all the unnecessary tests, which imply human being or animals, should be avoided, both for ethical and economic reasons. Indeed, these tests are very expensive and require a lot of time. The reduction of animal tests can be achieved developing alternative models, such as physical or mathematical models. Of course, the tests have to reproduce what happens in the human body as close to the reality as possible. Thus, the main goal of the research is to design and build devices able to reproduce the main physiological characteristics which influence the drug release.
Do you want to know more about dissolution tests and in vitro models? Read this
Do you want to know more about ADME processes and in silico models? Read this
Research lines
The TPP group deals with the study of drugs pharmacokinetics with a combined approach, analyzing both experimental and modeling aspects, to identify, quantify, and vary the key parameters that affect the blood concentration profile and improve the therapeutic effects. Our research can be summarized as:
Development and analysis of in vitro models (physical models)
- Analysis of the operative conditions influencing the release in conventional devices
- Study of the fluido-dynamic effect on the drug release
- Study of the dissolution medium effect on the drug release
- Development of a novel in vitro model simulating the human gastrointestinal tract
- Reproduction of the thermal history in the gastrointestinal tract
- Reproduction of the bio-chemical history in the gastrointestinal tract
- Reproduction of the stomach mechanical behavior
- Reproduction of mass exchange across the intestinal wall
Related publications:
Read More
2017
Cascone, Sara
Modeling and comparison of release profiles: Effect of the dissolution method Journal Article
European Journal of Pharmaceutical Sciences, 106 , pp. 352-361, 2017, ISSN: 0928-0987.
@article{Cascone2017,
title = {Modeling and comparison of release profiles: Effect of the dissolution method},
author = {Sara Cascone},
url = {http://www.sciencedirect.com/science/article/pii/S092809871730355X},
doi = {10.1016/j.ejps.2017.06.021},
issn = {0928-0987},
year = {2017},
date = {2017-08-30},
journal = {European Journal of Pharmaceutical Sciences},
volume = {106},
pages = {352-361},
abstract = {During the last decades, the study of the in vitro dissolution of pharmaceuticals has been strongly encouraged by the FDA in order to determine its relationship with the in vivo bioavailability of a drug. In this work immediate and extended release formulations containing diclofenac, a BCS class II drug, were studied using different dissolution methods. The release profiles obtained in USP Apparatus II and USP Apparatus IV were evaluated and compared to determine the effect of the fluid dynamic conditions on the release. The influence of the mixing conditions (i.e. the paddle rotation speed in USP Apparatus II or the inlet flow rate in USP Apparatus IV) on the drug release were evaluated, finding that, for the extended release formulations, they do not affect significantly the release profile. An in vitro device simulating the peristaltic contractions of the stomach during the digestion was used to simulate fluid dynamics closer to the real physiology. The tablets were found to behave in a completely different way if tested in the artificial stomach.
Both model-independent and model-dependent approaches were used to compare and fit the dissolution profiles, respectively. Fit factors were used as indicators of similarity of two dissolution profiles; model equations (such as zero-order, first-order, or Korsmeyer-Peppas equations) were used to fit the experimental data. With the identification of the best fitting model by the use of correlation factors and Akaike Information Criterion, the transport phenomena that determine the behavior of each formulation were identified.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
During the last decades, the study of the in vitro dissolution of pharmaceuticals has been strongly encouraged by the FDA in order to determine its relationship with the in vivo bioavailability of a drug. In this work immediate and extended release formulations containing diclofenac, a BCS class II drug, were studied using different dissolution methods. The release profiles obtained in USP Apparatus II and USP Apparatus IV were evaluated and compared to determine the effect of the fluid dynamic conditions on the release. The influence of the mixing conditions (i.e. the paddle rotation speed in USP Apparatus II or the inlet flow rate in USP Apparatus IV) on the drug release were evaluated, finding that, for the extended release formulations, they do not affect significantly the release profile. An in vitro device simulating the peristaltic contractions of the stomach during the digestion was used to simulate fluid dynamics closer to the real physiology. The tablets were found to behave in a completely different way if tested in the artificial stomach.
Both model-independent and model-dependent approaches were used to compare and fit the dissolution profiles, respectively. Fit factors were used as indicators of similarity of two dissolution profiles; model equations (such as zero-order, first-order, or Korsmeyer-Peppas equations) were used to fit the experimental data. With the identification of the best fitting model by the use of correlation factors and Akaike Information Criterion, the transport phenomena that determine the behavior of each formulation were identified.2016
Cascone, Sara; Lamberti, Gaetano; Marra, Francesco; Titomanlio, Giuseppe; d'Amore, Matteo; Barba, Anna Angela
Gastrointestinal behavior and ADME phenomena: I. In vitro simulation Journal Article
Journal of Drug Delivery Science and Technology, 35 , pp. 272-283, 2016, ISSN: 1773-2247.
@article{Cascone2016,
title = {Gastrointestinal behavior and ADME phenomena: I. In vitro simulation},
author = {Sara Cascone and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio and Matteo d'Amore and Anna Angela Barba},
url = {https://www.sciencedirect.com/science/article/pii/S1773224716302659
},
doi = {10.1016/j.jddst.2016.08.002},
issn = {1773-2247},
year = {2016},
date = {2016-10-01},
journal = {Journal of Drug Delivery Science and Technology},
volume = {35},
pages = {272-283},
abstract = {The most common administration route for pharmaceuticals is the oral one. A drug orally administered has to undergo several processes in order to carry out its therapeutic potential. The pharmaceutical has to dissolve and to release the API (Active Pharmaceutical Ingredient) in the desired location along the GI (Gastro Intestinal) tract, to pass through the intestinal wall, to overcome the liver (first-pass metabolism), and finally to reach the plasma, where it has to be stable during its travel toward the target organ/tissue. The key roles in this complex framework are played by the design (such as matrices, reservoirs, enteric systems) and the testing of the pharmaceuticals.
This review is focused on the state of the art in the pharmaceutical testing methods, carried out by the simulation of what happens once the pharmaceutical has been administered, investigating the in vitro approach. In the first section, the generalities of the dissolution and the ADME (Adsorption, Distribution, Metabolism and Excretion) phenomena are investigated. In the second section, the in vitro apparatuses are described, with a special focus on the role of food in their design and behavior. Some case histories of application for each approach are also discussed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The most common administration route for pharmaceuticals is the oral one. A drug orally administered has to undergo several processes in order to carry out its therapeutic potential. The pharmaceutical has to dissolve and to release the API (Active Pharmaceutical Ingredient) in the desired location along the GI (Gastro Intestinal) tract, to pass through the intestinal wall, to overcome the liver (first-pass metabolism), and finally to reach the plasma, where it has to be stable during its travel toward the target organ/tissue. The key roles in this complex framework are played by the design (such as matrices, reservoirs, enteric systems) and the testing of the pharmaceuticals.
This review is focused on the state of the art in the pharmaceutical testing methods, carried out by the simulation of what happens once the pharmaceutical has been administered, investigating the in vitro approach. In the first section, the generalities of the dissolution and the ADME (Adsorption, Distribution, Metabolism and Excretion) phenomena are investigated. In the second section, the in vitro apparatuses are described, with a special focus on the role of food in their design and behavior. Some case histories of application for each approach are also discussed.Piazza, Ornella; Cascone, Sara; Sessa, Linda; De Robertis, Edoardo ; Lamberti, Gaetano
The effect of liver esterases and temperature on remifentanil degradation in vitro Journal Article
International Journal of Pharmaceutics, 510 (1), pp. 359–364, 2016.
@article{Piazza2016b,
title = {The effect of liver esterases and temperature on remifentanil degradation in vitro},
author = {Ornella Piazza and Sara Cascone and Linda Sessa and Edoardo {De Robertis} and Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S0378517316305191},
doi = {10.1016/j.ijpharm.2016.06.043},
year = {2016},
date = {2016-07-04},
journal = {International Journal of Pharmaceutics},
volume = {510},
number = {1},
pages = {359\textendash364},
abstract = {Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo-sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients.The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed.Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo-sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients.The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed.Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures.2015
Cascone, Sara; Barba, Anna Angela; Lamberti, Gaetano; Marra, Francesco; Titomanlio, Giuseppe
Bioaccessibility of active principles: an in-vitro reproduction of human physiology Inproceedings
Proccedings of 4th International Conference on Food Digestion, pp. 1–1, 4th International Conference on Food Digestion, Naples, Italy, 2015.
@inproceedings{cascone2015b,
title = {Bioaccessibility of active principles: an in-vitro reproduction of human physiology},
author = { Sara Cascone and Anna Angela Barba and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio},
year = {2015},
date = {2015-03-01},
booktitle = {Proccedings of 4th International Conference on Food Digestion},
pages = {1--1},
publisher = {4th International Conference on Food Digestion},
address = {Naples, Italy},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
2014
Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Titomanlio, Giuseppe; Barba, Anna Angela
In-vitro models of the gastro-intestinal tract for pharmaceutical and nutritional purposes Inproceedings
Proceedings of CHISA 2014/PRES 2014, pp. 2–2, CHISA 2014, Prague, Czech Republic, 2014.
@inproceedings{s.2014-4,
title = {In-vitro models of the gastro-intestinal tract for pharmaceutical and nutritional purposes},
author = { Sara Cascone and Diego Caccavo and Gaetano Lamberti and Giuseppe Titomanlio and Anna Angela Barba},
year = {2014},
date = {2014-08-01},
booktitle = {Proceedings of CHISA 2014/PRES 2014},
pages = {2--2},
publisher = {CHISA 2014},
address = {Prague, Czech Republic},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Cascone, Sara; Lamberti, Gaetano; Marra, Francesco; Titomanlio, Giuseppe; Barba, Anna Angela
AN IN VITRO MODEL TO REPRODUCE THE MECHANICS AND THE ABSORPTION IN THE GASTROINTESTINAL TRACT Inproceedings
13th European Symposium on Controlled Drug Delivery, pp. 1–2, ESCDD 2014, Egmond aan Zee, The Netherlands, 2014.
@inproceedings{s.2014-1,
title = {AN IN VITRO MODEL TO REPRODUCE THE MECHANICS AND THE ABSORPTION IN THE GASTROINTESTINAL TRACT},
author = { Sara Cascone and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio and Anna Angela Barba},
year = {2014},
date = {2014-04-01},
booktitle = {13th European Symposium on Controlled Drug Delivery},
pages = {1--2},
publisher = {ESCDD 2014},
address = {Egmond aan Zee, The Netherlands},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Cascone, Sara; Barba, Anna Angela; Lamberti, Gaetano; Marra, Francesco; Titomanlio, Giuseppe
In-vitro reproduction of human physiology involved in bioaccessibility of drugs and nutrients Inproceedings
Proceedings of Conference of Food Engineering (CoFE), pp. 1–2, Conference of Food Engineering (CoFE), Omaha, Nebraska, 2014.
@inproceedings{cascone2014b,
title = {In-vitro reproduction of human physiology involved in bioaccessibility of drugs and nutrients},
author = { Sara Cascone and Anna Angela Barba and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio},
year = {2014},
date = {2014-04-01},
booktitle = {Proceedings of Conference of Food Engineering (CoFE)},
pages = {1--2},
publisher = {Conference of Food Engineering (CoFE)},
address = {Omaha, Nebraska},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
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Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe
Simulation of gastrointestinal tract: mechanics and absorption Inproceedings
Proceedings of PBP 2014, pp. 3–4, PBP 2014, Lisbon, Portugal, 2014.
@inproceedings{s.2014-2,
title = {Simulation of gastrointestinal tract: mechanics and absorption},
author = { Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio},
year = {2014},
date = {2014-03-01},
booktitle = {Proceedings of PBP 2014},
pages = {3--4},
publisher = {PBP 2014},
address = {Lisbon, Portugal},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
2012
Lamberti, Gaetano; Cascone, Sara; Iannaccone, Margherita; Titomanlio, Giuseppe
In vitro simulation of drug intestinal absorption. Journal Article
International journal of pharmaceutics, 439 (1-2), pp. 165–8, 2012, ISSN: 1873-3476.
@article{Lamberti2012d,
title = {In vitro simulation of drug intestinal absorption.},
author = { Gaetano Lamberti and Sara Cascone and Margherita Iannaccone and Giuseppe Titomanlio},
url = {http://www.sciencedirect.com/science/article/pii/S0378517312009520},
doi = {10.1016/j.ijpharm.2012.10.012},
issn = {1873-3476},
year = {2012},
date = {2012-12-01},
journal = {International journal of pharmaceutics},
volume = {439},
number = {1-2},
pages = {165--8},
abstract = {In this work, a simple set-up was designed, realized and tested to evaluate the effect of intestinal absorption on the in vitro drug release studies. The conventional USP-approved dissolution apparatus 2 was equipped with an hollow fibers filter, along with the necessary tubing and pumps, to simulate the two-fluids real behavior (the gastro intestinal lumen and the gastro intestinal circulatory system). The realized set-up was characterized in term of mass exchange characteristic, using the theophylline as the model drug, also with the aid of a simple mathematical model; then the release kinetics of a controlled release tablet was evaluated in the conventional test as well as in the novel simulator. The concentration of drug in the release compartment (which simulates the gastric lumen) was found lower in the novel simulator than in the traditional one.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this work, a simple set-up was designed, realized and tested to evaluate the effect of intestinal absorption on the in vitro drug release studies. The conventional USP-approved dissolution apparatus 2 was equipped with an hollow fibers filter, along with the necessary tubing and pumps, to simulate the two-fluids real behavior (the gastro intestinal lumen and the gastro intestinal circulatory system). The realized set-up was characterized in term of mass exchange characteristic, using the theophylline as the model drug, also with the aid of a simple mathematical model; then the release kinetics of a controlled release tablet was evaluated in the conventional test as well as in the novel simulator. The concentration of drug in the release compartment (which simulates the gastric lumen) was found lower in the novel simulator than in the traditional one.Cascone, Sara; Lamberti, Gaetano; Paolucci, Fabio; Titomanlio, Giuseppe
In vitro and in silico approaches to reproduce pharmacokinetic relevant phenomena Inproceedings
Proceedings of 8th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, pp. 1–2, PBP 2012, Istanbul, Turkey, 2012.
@inproceedings{s.2012,
title = {In vitro and in silico approaches to reproduce pharmacokinetic relevant phenomena},
author = { Sara Cascone and Gaetano Lamberti and Fabio Paolucci and Giuseppe Titomanlio},
year = {2012},
date = {2012-03-01},
booktitle = {Proceedings of 8th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology},
pages = {1--2},
publisher = {PBP 2012},
address = {Istanbul, Turkey},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
2011
Cascone, Sara; Santis, Felice De; Lamberti, Gaetano; Titomanlio, Giuseppe
The influence of dissolution conditions on the drug ADME phenomena. Journal Article
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V, 79 (2), pp. 382–91, 2011, ISSN: 1873-3441.
@article{Cascone2011,
title = {The influence of dissolution conditions on the drug ADME phenomena.},
author = { Sara Cascone and Felice De Santis and Gaetano Lamberti and Giuseppe Titomanlio},
url = {http://www.sciencedirect.com/science/article/pii/S093964111100141X},
doi = {10.1016/j.ejpb.2011.04.003},
issn = {1873-3441},
year = {2011},
date = {2011-10-01},
journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft f\"{u}r Pharmazeutische Verfahrenstechnik e.V},
volume = {79},
number = {2},
pages = {382--91},
abstract = {In this work, a review of the apparatuses available to mimic what happens to a drug (or to foodstuffs) once ingested is presented. Similarly, a brief review of the models proposed to simulate the fate of a drug administered to a living body is reported. Then, the release kinetics of extended release of diclofenac from a commercial enteric-coated tablet was determined both in a conventional dissolution tester (USP Apparatus 2, Method A) as well as in an apparatus modified to reproduce a given pH evolution, closer to the real one than the one suggested by USP. The two experimental release profiles were reported and discussed; therefore, they were adopted as input functions for a previously proposed pharmacokinetic model. The obtained evolutions with time of plasma concentration were presented and used to assess the effectiveness of the commercial pharmaceutical products. The importance of a correct in vitro simulation for the design of pharmaceutical dosage systems was thus emphasized.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this work, a review of the apparatuses available to mimic what happens to a drug (or to foodstuffs) once ingested is presented. Similarly, a brief review of the models proposed to simulate the fate of a drug administered to a living body is reported. Then, the release kinetics of extended release of diclofenac from a commercial enteric-coated tablet was determined both in a conventional dissolution tester (USP Apparatus 2, Method A) as well as in an apparatus modified to reproduce a given pH evolution, closer to the real one than the one suggested by USP. The two experimental release profiles were reported and discussed; therefore, they were adopted as input functions for a previously proposed pharmacokinetic model. The obtained evolutions with time of plasma concentration were presented and used to assess the effectiveness of the commercial pharmaceutical products. The importance of a correct in vitro simulation for the design of pharmaceutical dosage systems was thus emphasized.
Development and analysis of in silico models (mathematical models)
- Development of simple models
- Divide the human body in compartments that do not take into account physiology
- Development of multi-compartimental models
- Development of physiologically based models
- Divide the human body in compartments, each with a specific function
- Identify the main transport phenomena in each compartment
- Identify the pharmacokinetic model parameters in each compartment and personalize them on the basis of the patient characteristics
- Simulate the plasmatic concentrations starting from the in vitro data obtained
Related publications:
2017
Cascone, Sara
Modeling and comparison of release profiles: Effect of the dissolution method Journal Article
European Journal of Pharmaceutical Sciences, 106 , pp. 352-361, 2017, ISSN: 0928-0987.
@article{Cascone2017,
title = {Modeling and comparison of release profiles: Effect of the dissolution method},
author = {Sara Cascone},
url = {http://www.sciencedirect.com/science/article/pii/S092809871730355X},
doi = {10.1016/j.ejps.2017.06.021},
issn = {0928-0987},
year = {2017},
date = {2017-08-30},
journal = {European Journal of Pharmaceutical Sciences},
volume = {106},
pages = {352-361},
abstract = {During the last decades, the study of the in vitro dissolution of pharmaceuticals has been strongly encouraged by the FDA in order to determine its relationship with the in vivo bioavailability of a drug. In this work immediate and extended release formulations containing diclofenac, a BCS class II drug, were studied using different dissolution methods. The release profiles obtained in USP Apparatus II and USP Apparatus IV were evaluated and compared to determine the effect of the fluid dynamic conditions on the release. The influence of the mixing conditions (i.e. the paddle rotation speed in USP Apparatus II or the inlet flow rate in USP Apparatus IV) on the drug release were evaluated, finding that, for the extended release formulations, they do not affect significantly the release profile. An in vitro device simulating the peristaltic contractions of the stomach during the digestion was used to simulate fluid dynamics closer to the real physiology. The tablets were found to behave in a completely different way if tested in the artificial stomach.
Both model-independent and model-dependent approaches were used to compare and fit the dissolution profiles, respectively. Fit factors were used as indicators of similarity of two dissolution profiles; model equations (such as zero-order, first-order, or Korsmeyer-Peppas equations) were used to fit the experimental data. With the identification of the best fitting model by the use of correlation factors and Akaike Information Criterion, the transport phenomena that determine the behavior of each formulation were identified.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
During the last decades, the study of the in vitro dissolution of pharmaceuticals has been strongly encouraged by the FDA in order to determine its relationship with the in vivo bioavailability of a drug. In this work immediate and extended release formulations containing diclofenac, a BCS class II drug, were studied using different dissolution methods. The release profiles obtained in USP Apparatus II and USP Apparatus IV were evaluated and compared to determine the effect of the fluid dynamic conditions on the release. The influence of the mixing conditions (i.e. the paddle rotation speed in USP Apparatus II or the inlet flow rate in USP Apparatus IV) on the drug release were evaluated, finding that, for the extended release formulations, they do not affect significantly the release profile. An in vitro device simulating the peristaltic contractions of the stomach during the digestion was used to simulate fluid dynamics closer to the real physiology. The tablets were found to behave in a completely different way if tested in the artificial stomach.
Both model-independent and model-dependent approaches were used to compare and fit the dissolution profiles, respectively. Fit factors were used as indicators of similarity of two dissolution profiles; model equations (such as zero-order, first-order, or Korsmeyer-Peppas equations) were used to fit the experimental data. With the identification of the best fitting model by the use of correlation factors and Akaike Information Criterion, the transport phenomena that determine the behavior of each formulation were identified.2016
Lamberti, Gaetano; Cascone, Sara; Marra, Francesco; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela
Gastrointestinal behavior and ADME phenomena: II. in silico simulation Journal Article
Journal of Drug Delivery Science and Technology, 35 , pp. 165-171, 2016, ISSN: 1773-2247.
@article{Lamberti2016,
title = {Gastrointestinal behavior and ADME phenomena: II. in silico simulation},
author = {Gaetano Lamberti and Sara Cascone and Francesco Marra and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba},
url = {http://www.sciencedirect.com/science/article/pii/S1773224716302118},
doi = {10.1016/j.jddst.2016.06.014},
issn = {1773-2247},
year = {2016},
date = {2016-07-04},
journal = {Journal of Drug Delivery Science and Technology},
volume = {35},
pages = {165-171},
abstract = {The main goal of the pharmacokinetic modeling is the prediction of the drug concentration in the blood, tissues, and organs. The approaches to the modeling of physiological phenomena can be different on the basis of the details used to describe the Adsorption, Distribution, Metabolism, and Excretion (ADME) phenomena.
This review is focused on the state of the art in the pharmacokinetic modeling, on the different approaches used to describe the drug fate once it is administered. In particular, the early and the recent developments in the pharmacokinetic and in the gastrointestinal behavior modeling are discussed, together with some case histories of their applications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The main goal of the pharmacokinetic modeling is the prediction of the drug concentration in the blood, tissues, and organs. The approaches to the modeling of physiological phenomena can be different on the basis of the details used to describe the Adsorption, Distribution, Metabolism, and Excretion (ADME) phenomena.
This review is focused on the state of the art in the pharmacokinetic modeling, on the different approaches used to describe the drug fate once it is administered. In particular, the early and the recent developments in the pharmacokinetic and in the gastrointestinal behavior modeling are discussed, together with some case histories of their applications.Abbiati, Roberto Andrea; Lamberti, Gaetano; Grassi, Mario; Trotta, Francesco; Manca, Davide
Definition and validation of a patient-individualized physiologically-based pharmacokinetic model Journal Article
Computers & Chemical Engineering, 84 , pp. 394-408, 2016, ISSN: 00981354.
@article{Abbiati2015,
title = {Definition and validation of a patient-individualized physiologically-based pharmacokinetic model},
author = { Roberto Andrea Abbiati and Gaetano Lamberti and Mario Grassi and Francesco Trotta and Davide Manca},
url = {http://www.sciencedirect.com/science/article/pii/S0098135415003130},
doi = {10.1016/j.compchemeng.2015.09.018},
issn = {00981354},
year = {2016},
date = {2016-01-04},
journal = {Computers & Chemical Engineering},
volume = {84 },
pages = {394-408},
abstract = {Pharmacokinetic modeling based on a mechanistic approach is a promising tool for drug concentration prediction in living beings. The development of a reduced physiologically-based pharmacokinetic model (PBPK model), is performed by lumping organs and tissues with comparable characteristics respect to drug distribution phenomena. The proposed reduced model comprises eight differential equations and 18 adaptive parameters. To improve the quality of the PBPK model these adaptive parameters are alternatively: (i) individualized according to literature correlations on the physiological features of each patient; (ii) assigned as constants based on the features of either human body or drug properties; (iii) regressed respect to experimental data. The model predictive capability is validated with experimental blood concentrations of remifentanil, an analgesic drug, administered via bolus injection with four doses (2, 5, 15, 30$mu$g/kg) to mixed groups of patients. Concentration profiles for the four simulated doses reveal a rather good consistency with experimental data.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pharmacokinetic modeling based on a mechanistic approach is a promising tool for drug concentration prediction in living beings. The development of a reduced physiologically-based pharmacokinetic model (PBPK model), is performed by lumping organs and tissues with comparable characteristics respect to drug distribution phenomena. The proposed reduced model comprises eight differential equations and 18 adaptive parameters. To improve the quality of the PBPK model these adaptive parameters are alternatively: (i) individualized according to literature correlations on the physiological features of each patient; (ii) assigned as constants based on the features of either human body or drug properties; (iii) regressed respect to experimental data. The model predictive capability is validated with experimental blood concentrations of remifentanil, an analgesic drug, administered via bolus injection with four doses (2, 5, 15, 30$mu$g/kg) to mixed groups of patients. Concentration profiles for the four simulated doses reveal a rather good consistency with experimental data.2015
Cascone, Sara; Piazza, Ornella; Lamberti, Gaetano; Barba, Anna Angela; Abbiati, Roberto Andrea; Manca, Davide
PHARMACOKINETICS OF REMIFENTANIL: METABOLISM AND MODELING Inproceedings
1st International Congress of Controlled Release Society - Greek Local Chapter, 2015.
@inproceedings{Cascone:aa,
title = {PHARMACOKINETICS OF REMIFENTANIL: METABOLISM AND MODELING},
author = {Sara Cascone and Ornella Piazza and Gaetano Lamberti and Anna Angela Barba and Roberto Andrea Abbiati and Davide Manca},
year = {2015},
date = {2015-05-27},
booktitle = {1st International Congress of Controlled Release Society - Greek Local Chapter},
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Abbiati, Roberto Andrea; Lamberti, Gaetano; Barba, Anna Angela; Grassi, Mario; Manca, Davide
A PSE approach to patient-individualized physiologically-based pharmacokinetic modeling Journal Article
12th International Symposium on Process Systems Engineering and 25th European Symposium on Computer Aided Process Engineering, 37 , pp. 77–84, 2015, ISSN: 15707946.
@article{Abbiati2015a,
title = {A PSE approach to patient-individualized physiologically-based pharmacokinetic modeling},
author = { Roberto Andrea Abbiati and Gaetano Lamberti and Anna Angela Barba and Mario Grassi and Davide Manca},
url = {http://www.sciencedirect.com/science/article/pii/B9780444635785500104},
doi = {10.1016/B978-0-444-63578-5.50010-4},
issn = {15707946},
year = {2015},
date = {2015-01-01},
journal = {12th International Symposium on Process Systems Engineering and 25th European Symposium on Computer Aided Process Engineering},
volume = {37},
pages = {77--84},
publisher = {Elsevier},
series = {Computer Aided Chemical Engineering},
abstract = {Pharmacokinetic modeling allows predicting the drug concentration reached in the blood as a consequence of a specific administration. When such models are based on mammalian anatomy and physiology it is possible to theoretically evaluate the drug concentration in every organ and tissue of the body. This is the case of the so-called physiologically based pharmacokinetic (PBPK) models. This paper proposes and validates a procedure to deploy PBPK models based on a simplified, although highly consistent with human anatomy and physiology, approach. The article aims at reducing the pharmacokinetic variations among subjects due to inter-individual variability, by applying a strategy to individualize some model parameters. The simulation results are validated respect to experimental data on remifentanil.},
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Pharmacokinetic modeling allows predicting the drug concentration reached in the blood as a consequence of a specific administration. When such models are based on mammalian anatomy and physiology it is possible to theoretically evaluate the drug concentration in every organ and tissue of the body. This is the case of the so-called physiologically based pharmacokinetic (PBPK) models. This paper proposes and validates a procedure to deploy PBPK models based on a simplified, although highly consistent with human anatomy and physiology, approach. The article aims at reducing the pharmacokinetic variations among subjects due to inter-individual variability, by applying a strategy to individualize some model parameters. The simulation results are validated respect to experimental data on remifentanil.2014
Del Cont, Renzo ; Abrami, Michela; Hasa, Dritan; Perissutti, Beatrice; Voinovich, Dario; Barba, Anna Angela; Lamberti, Gaetano; Grassi, Gabriele; Colombo, Italo; Manca, Davide; Grassi, Mario
A physiologically oriented mathematical model for the description of in vivo drug release and absorption Journal Article
ADMET & DMPK, 2 (2), pp. 80–97, 2014, ISSN: 1848-7718.
@article{del2014physiologically,
title = {A physiologically oriented mathematical model for the description of in vivo drug release and absorption},
author = {Renzo {Del Cont} and Michela Abrami and Dritan Hasa and Beatrice Perissutti and Dario Voinovich and Anna Angela Barba and Gaetano Lamberti and Gabriele Grassi and Italo Colombo and Davide Manca and Mario Grassi},
url = {http://pub.iapchem.org/ojs/index.php/admet/article/view/34},
doi = {10.5599/admet.2.2.34},
issn = {1848-7718},
year = {2014},
date = {2014-07-01},
journal = {ADMET & DMPK},
volume = {2},
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abstract = {This paper focuses on a physiologically-oriented mathematical model aimed at studying the in vivo drug release, absorption, distribution, metabolism and elimination (ADME). To this purpose, the model accounts for drug delivery from an ensemble of non-eroding poly-disperse polymeric particles and the subsequent ADME processes. The model outcomes are studied with reference to three widely used drugs: theophylline, temazepam and nimesulide. One of the most important results of this study is the quantitative evaluation of the interplay between the release kinetics and the subsequent ADME processes. Indeed, it is usually assumed that in vivo drug release coincides with in vitro so that the effect exerted by the ADME processes is neglected. In addition, the proposed model may be an important tool for the design of delivery systems since, through proper changes, it could also account for different oral delivery systems.},
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This paper focuses on a physiologically-oriented mathematical model aimed at studying the in vivo drug release, absorption, distribution, metabolism and elimination (ADME). To this purpose, the model accounts for drug delivery from an ensemble of non-eroding poly-disperse polymeric particles and the subsequent ADME processes. The model outcomes are studied with reference to three widely used drugs: theophylline, temazepam and nimesulide. One of the most important results of this study is the quantitative evaluation of the interplay between the release kinetics and the subsequent ADME processes. Indeed, it is usually assumed that in vivo drug release coincides with in vitro so that the effect exerted by the ADME processes is neglected. In addition, the proposed model may be an important tool for the design of delivery systems since, through proper changes, it could also account for different oral delivery systems.2013
Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe; Piazza, Ornella
Pharmacokinetics of Remifentanil: a three-compartmental modeling approach Journal Article
Translational Medicine @ UniSa, 7 , pp. 18–22, 2013, ISSN: 2239-9747.
@article{Cascone2013,
title = {Pharmacokinetics of Remifentanil: a three-compartmental modeling approach},
author = { Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio and Ornella Piazza},
url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829787/},
issn = {2239-9747},
year = {2013},
date = {2013-09-01},
journal = {Translational Medicine @ UniSa},
volume = {7},
pages = {18--22},
publisher = {Universit},
abstract = {Remifentanil is a new opioid derivative drug characterized by a fast onset and by a short time of action, since it is rapidly degraded by esterases in blood and other tissues. Its pharmacokinetic and pharmacodynamics properties make remifentanil a very interesting molecule in the field of 0anesthesia. However a complete and versatile pharmacokinetic description of remifentanil still lacks. In this work a three-compartmental model has been developed to describe the pharmacokinetics of remifentanil both in the case in which it is administered by intravenous constant-rate infusion and by bolus injection. The model curves have been compared with experimental data published in scientific papers and the model parameters have been optimized to describe both ways of administration. The ad hoc model is adaptable and potentially useful for predictive purposes.},
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Remifentanil is a new opioid derivative drug characterized by a fast onset and by a short time of action, since it is rapidly degraded by esterases in blood and other tissues. Its pharmacokinetic and pharmacodynamics properties make remifentanil a very interesting molecule in the field of 0anesthesia. However a complete and versatile pharmacokinetic description of remifentanil still lacks. In this work a three-compartmental model has been developed to describe the pharmacokinetics of remifentanil both in the case in which it is administered by intravenous constant-rate infusion and by bolus injection. The model curves have been compared with experimental data published in scientific papers and the model parameters have been optimized to describe both ways of administration. The ad hoc model is adaptable and potentially useful for predictive purposes.Lamberti, Gaetano
Industrial Engineering & Translational Medicine: The Role of Modeling Journal Article
Industrial Engineering & Management, 02 (01), pp. e112, 2013, ISSN: 21690316.
@article{Lamberti2013,
title = {Industrial Engineering & Translational Medicine: The Role of Modeling},
author = { Gaetano Lamberti},
url = {http://www.omicsgroup.org/journals/industrial-engineering-translational-medicine-the-role-of-modeling-2169-0316.1000e112.php?aid=9217},
doi = {10.4172/2169-0316.1000e112},
issn = {21690316},
year = {2013},
date = {2013-01-01},
journal = {Industrial Engineering & Management},
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2012
Cascone, Sara; Lamberti, Gaetano; Paolucci, Fabio; Titomanlio, Giuseppe
In vitro and in silico approaches to reproduce pharmacokinetic relevant phenomena Inproceedings
Proceedings of 8th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, pp. 1–2, PBP 2012, Istanbul, Turkey, 2012.
@inproceedings{s.2012,
title = {In vitro and in silico approaches to reproduce pharmacokinetic relevant phenomena},
author = { Sara Cascone and Gaetano Lamberti and Fabio Paolucci and Giuseppe Titomanlio},
year = {2012},
date = {2012-03-01},
booktitle = {Proceedings of 8th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology},
pages = {1--2},
publisher = {PBP 2012},
address = {Istanbul, Turkey},
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Lamberti, Gaetano; Cascone, Sara; Titomanlio, Giuseppe
An engineering approach to biomedical sciences: advanced testing methods and pharmacokinetic modeling Journal Article
Translational Medicine@ UniSa, 4 , pp. 34–38, 2012.
@article{Lamberti2012b,
title = {An engineering approach to biomedical sciences: advanced testing methods and pharmacokinetic modeling},
author = { Gaetano Lamberti and Sara Cascone and Giuseppe Titomanlio},
year = {2012},
date = {2012-01-01},
journal = {Translational Medicine@ UniSa},
volume = {4},
pages = {34--38},
publisher = {Universit},
abstract = {In this paper, the philosophy of a research in pharmacology field, driven by an engineering approach, was described along with some case histories and examples. The improvement in the testing methods for pharmaceutical systems (in-vitro techniques), as well as the proposal and the testing of mathematical models to describe the pharmacokinetics (in-silico techniques) are reported with the aim of pointing out methodologies and tools able to reduce the need of expensive and ethical problematic in-vivo measurements.},
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In this paper, the philosophy of a research in pharmacology field, driven by an engineering approach, was described along with some case histories and examples. The improvement in the testing methods for pharmaceutical systems (in-vitro techniques), as well as the proposal and the testing of mathematical models to describe the pharmacokinetics (in-silico techniques) are reported with the aim of pointing out methodologies and tools able to reduce the need of expensive and ethical problematic in-vivo measurements.2011
Grassi, Mario; Lamberti, Gaetano; Cascone, Sara; Grassi, Gabriele
Mathematical modeling of simultaneous drug release and in vivo absorption. Journal Article
International journal of pharmaceutics, 418 (1), pp. 130–41, 2011, ISSN: 1873-3476.
@article{Grassi2011,
title = {Mathematical modeling of simultaneous drug release and in vivo absorption.},
author = { Mario Grassi and Gaetano Lamberti and Sara Cascone and Gabriele Grassi},
url = {http://www.sciencedirect.com/science/article/pii/S0378517311000275},
doi = {10.1016/j.ijpharm.2010.12.044},
issn = {1873-3476},
year = {2011},
date = {2011-10-01},
journal = {International journal of pharmaceutics},
volume = {418},
number = {1},
pages = {130--41},
abstract = {The attention of this review is focussed on the mathematical modeling of the simultaneous processes of drug release and absorption/distribution/metabolism/elimination (ADME processes) following different administration routes. Among all of them, for their clinical importance, the oral, transdermal and local delivery are considered. The bases of the presented mathematical models are shown after the discussion of the most relevant phenomena characterising the particular administration route considered. Then, model performances are compared to experimental evidences in order to evaluate their reliability and soundness. The most important conclusion of this review is that despite the complexity of the problem involved in the description of the fate of the drugs after their administration, the scientific community is close to the solution as witnessed by the various interesting and promising approaches here presented about the oral, transdermal and local administration routes.},
keywords = {},
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The attention of this review is focussed on the mathematical modeling of the simultaneous processes of drug release and absorption/distribution/metabolism/elimination (ADME processes) following different administration routes. Among all of them, for their clinical importance, the oral, transdermal and local delivery are considered. The bases of the presented mathematical models are shown after the discussion of the most relevant phenomena characterising the particular administration route considered. Then, model performances are compared to experimental evidences in order to evaluate their reliability and soundness. The most important conclusion of this review is that despite the complexity of the problem involved in the description of the fate of the drugs after their administration, the scientific community is close to the solution as witnessed by the various interesting and promising approaches here presented about the oral, transdermal and local administration routes.Cascone, Sara; Santis, Felice De; Lamberti, Gaetano; Titomanlio, Giuseppe
The influence of dissolution conditions on the drug ADME phenomena. Journal Article
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V, 79 (2), pp. 382–91, 2011, ISSN: 1873-3441.
@article{Cascone2011,
title = {The influence of dissolution conditions on the drug ADME phenomena.},
author = { Sara Cascone and Felice De Santis and Gaetano Lamberti and Giuseppe Titomanlio},
url = {http://www.sciencedirect.com/science/article/pii/S093964111100141X},
doi = {10.1016/j.ejpb.2011.04.003},
issn = {1873-3441},
year = {2011},
date = {2011-10-01},
journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft f\"{u}r Pharmazeutische Verfahrenstechnik e.V},
volume = {79},
number = {2},
pages = {382--91},
abstract = {In this work, a review of the apparatuses available to mimic what happens to a drug (or to foodstuffs) once ingested is presented. Similarly, a brief review of the models proposed to simulate the fate of a drug administered to a living body is reported. Then, the release kinetics of extended release of diclofenac from a commercial enteric-coated tablet was determined both in a conventional dissolution tester (USP Apparatus 2, Method A) as well as in an apparatus modified to reproduce a given pH evolution, closer to the real one than the one suggested by USP. The two experimental release profiles were reported and discussed; therefore, they were adopted as input functions for a previously proposed pharmacokinetic model. The obtained evolutions with time of plasma concentration were presented and used to assess the effectiveness of the commercial pharmaceutical products. The importance of a correct in vitro simulation for the design of pharmaceutical dosage systems was thus emphasized.},
keywords = {},
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In this work, a review of the apparatuses available to mimic what happens to a drug (or to foodstuffs) once ingested is presented. Similarly, a brief review of the models proposed to simulate the fate of a drug administered to a living body is reported. Then, the release kinetics of extended release of diclofenac from a commercial enteric-coated tablet was determined both in a conventional dissolution tester (USP Apparatus 2, Method A) as well as in an apparatus modified to reproduce a given pH evolution, closer to the real one than the one suggested by USP. The two experimental release profiles were reported and discussed; therefore, they were adopted as input functions for a previously proposed pharmacokinetic model. The obtained evolutions with time of plasma concentration were presented and used to assess the effectiveness of the commercial pharmaceutical products. The importance of a correct in vitro simulation for the design of pharmaceutical dosage systems was thus emphasized.2010
Muria, Michela Di; Lamberti, Gaetano; Titomanlio, Giuseppe
Physiologically Based Pharmacokinetics: A Simple, All Purpose Model Journal Article
Industrial & Engineering Chemistry Research, 49 (6), pp. 2969–2978, 2010, ISSN: 0888-5885.
@article{DiMuria2010,
title = {Physiologically Based Pharmacokinetics: A Simple, All Purpose Model},
author = { Michela Di Muria and Gaetano Lamberti and Giuseppe Titomanlio},
url = {http://pubs.acs.org/doi/abs/10.1021/ie9015717},
doi = {10.1021/ie9015717},
issn = {0888-5885},
year = {2010},
date = {2010-03-01},
journal = {Industrial & Engineering Chemistry Research},
volume = {49},
number = {6},
pages = {2969--2978},
publisher = {American Chemical Society},
abstract = {To predict the drug hemeatic levels after administration is a goal of great interest in the design of novel pharmaceutical systems and in therapies management. The most reliable approach in pharmacokinetic modeling consists in analyzing the physiology of the living beings and in describing tissues and organs as different biochemical reactors. These models have been identified as physiologically based pharmacokinetic models (PBPK). They can be very detailed in the description, but, in this case, they also claim for the knowledge of an high number of parameters which are difficult to be determined by experiments. In this work, a review of the most complete PBPK models proposed in literature was performed, and a novel PBPK model was developed and validated by comparison with in vivo data available in the literature. The appeals of the novel model are its simplicity and the limited number of parameters required. Last but not least, it was proved able to predict the hemeatic drug levels after different kinds of administrations (intravenous injection, oral assumption of delayed release tablets).},
keywords = {},
pubstate = {published},
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To predict the drug hemeatic levels after administration is a goal of great interest in the design of novel pharmaceutical systems and in therapies management. The most reliable approach in pharmacokinetic modeling consists in analyzing the physiology of the living beings and in describing tissues and organs as different biochemical reactors. These models have been identified as physiologically based pharmacokinetic models (PBPK). They can be very detailed in the description, but, in this case, they also claim for the knowledge of an high number of parameters which are difficult to be determined by experiments. In this work, a review of the most complete PBPK models proposed in literature was performed, and a novel PBPK model was developed and validated by comparison with in vivo data available in the literature. The appeals of the novel model are its simplicity and the limited number of parameters required. Last but not least, it was proved able to predict the hemeatic drug levels after different kinds of administrations (intravenous injection, oral assumption of delayed release tablets).2009
Muria, Michela Di; Lamberti, Gaetano; Titomanlio, Giuseppe
Physiologically based pharmacokinetic modeling of immediate and delayed release dosage forms Inproceedings
Proceedings of CRS, pp. 1–4, Copenhagen, Danimarca, 2009.
@inproceedings{di2009,
title = {Physiologically based pharmacokinetic modeling of immediate and delayed release dosage forms},
author = { Michela Di Muria and Gaetano Lamberti and Giuseppe Titomanlio},
year = {2009},
date = {2009-07-01},
booktitle = {Proceedings of CRS},
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Muria, Michela Di; Lamberti, Gaetano; Titomanlio, Giuseppe
Modeling the pharmacokinetics of extended release pharmaceutical systems Journal Article
Heat and Mass Transfer, 45 (5), pp. 579–589, 2009, ISSN: 0947-7411.
@article{DiMuria2009a,
title = {Modeling the pharmacokinetics of extended release pharmaceutical systems},
author = { Michela Di Muria and Gaetano Lamberti and Giuseppe Titomanlio},
url = {http://link.springer.com/10.1007/s00231-008-0456-7},
doi = {10.1007/s00231-008-0456-7},
issn = {0947-7411},
year = {2009},
date = {2009-03-01},
journal = {Heat and Mass Transfer},
volume = {45},
number = {5},
pages = {579--589},
publisher = {Springer-Verlag},
abstract = {The pharmacokinetic (PK) models predict the hematic concentration of drugs after the administration. In compartment modeling, the body is described by a set of interconnected “vessels” or “compartments”; the modeling consisting of transient mass balances. Usually the orally administered drugs were considered as immediately available: this cannot describe the administration of extended-release systems. In this work we added to the traditional compartment models the ability to account for a delay in administration, relating this delay to in vitro data. Firstly, the method was validated, applying the model to the dosage of nicotine by chewing-gum; the model was tuned by in vitro/in vivo data of drugs (divalproex-sodium and diltiazem) with medium-rate release kinetics, then it was applied in describing in vivo evolutions due to the assumption of fast- and slow-release systems. The model reveals itself predictive, the same of a Level A in vitro/in vivo correlation, but being physically based, it is preferable to a purely statistical method.},
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The pharmacokinetic (PK) models predict the hematic concentration of drugs after the administration. In compartment modeling, the body is described by a set of interconnected “vessels” or “compartments”; the modeling consisting of transient mass balances. Usually the orally administered drugs were considered as immediately available: this cannot describe the administration of extended-release systems. In this work we added to the traditional compartment models the ability to account for a delay in administration, relating this delay to in vitro data. Firstly, the method was validated, applying the model to the dosage of nicotine by chewing-gum; the model was tuned by in vitro/in vivo data of drugs (divalproex-sodium and diltiazem) with medium-rate release kinetics, then it was applied in describing in vivo evolutions due to the assumption of fast- and slow-release systems. The model reveals itself predictive, the same of a Level A in vitro/in vivo correlation, but being physically based, it is preferable to a purely statistical method.Muria, Michela Di; Lamberti, Gaetano
Un modello farmacocinetico fisiologico, semplice ed efficace Journal Article
NCF-Notiziario Chimico Farmaceutico, 48 (6), pp. 50–53, 2009, ISSN: 0393-3733.
@article{DiMuria2009,
title = {Un modello farmacocinetico fisiologico, semplice ed efficace},
author = { Michela Di Muria and Gaetano Lamberti},
issn = {0393-3733},
year = {2009},
date = {2009-01-01},
journal = {NCF-Notiziario Chimico Farmaceutico},
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2007
Lamberti, Gaetano; Muria, Michela Di; Titomanlio, Giuseppe
Modeling the pharmacokinetics of Extended Release pharmaceutical systems Inproceedings
Proceedings of European Congress of Chemical Engineering (ECCE-6), pp. 381–382, Copenhagen, 2007.
@inproceedings{lamberti2007,
title = {Modeling the pharmacokinetics of Extended Release pharmaceutical systems},
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booktitle = {Proceedings of European Congress of Chemical Engineering (ECCE-6)},
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