@article{Caccavo2023,

title = {Impact of drug release in USP II and in-vitro stomach on pharmacokinetic: The case study of immediate-release carbamazepine tablets},

author = {Diego Caccavo and Marco Iannone and Anna Angela Barba and Gaetano Lamberti},

url = {https://www.sciencedirect.com/science/article/pii/S0009250922009563},

doi = {10.1016/j.ces.2022.118371},

year  = {2023},

date = {2023-03-05},

journal = {Chemical Engineering Science},

volume = {267},

abstract = {The in-vitro reproduction of the real physiological conditions that occur along the gastrointestinal (GI) tract would be the optimum for the dissolution and release testing of pharmaceutical formulations for oral intake. In this study a method for the automated reproduction of the real pH conditions that occurs in the gastric cavity and a device that mimics the same forces exerted by the internal walls of the stomach are presented. Commercial immediate-release carbamazepine tablets were tested in conventional (USP II) and unconventional apparatuses. The gastric pH and the fluid dynamic conditions are factors to be carefully considered since they both affect the drug release profiles. Finally, a PBPK model was used to predict the evolution of plasma drug concentrations knowing the experimental in-vitro GI release behavior. It was found that, for immediate-release carbamazepine tablet, the gastric drug release does not have a major impact on the plasmatic drug concentration.},

keywords = {Drug Delivery Systems, Mathematical modeling, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Cascone2018,

title = {A physiologically-based model to predict individual pharmacokinetics and pharmacodynamics of remifentanil},

author = {Sara Cascone and Gaetano Lamberti and Ornella Piazza and Roberto Andrea Abbiati and Davide Manca},

url = {http://www.sciencedirect.com/science/article/pii/S0928098717305201},

doi = {10.1016/j.ejps.2017.09.028},

issn = {0928-0987},

year  = {2018},

date = {2018-01-01},

journal = {European Journal of Pharmaceutical Sciences},

volume = {111},

pages = {20-28},

abstract = {Remifentanil based anesthesia is nowadays spread worldwide. This drug is characterized by a rapid onset of the analgesic effects, but also by a rapid onset of the side effects. For this reason, the knowledge of the remifentanil concentration in the human body is a key topic in anesthesiology. The aims of this work are to propose and validate a physiologically based pharmacokinetic model capable to predict both the pharmacokinetics and pharmacodynamics of remifentanil, and to take into account the inter-individual differences among the patients (such as height and body mass). The blood concentration of remifentanil has been successfully simulated and compared with experimental literature data. The pharmacodynamics, in terms of effect of remifentanil on minute ventilation and electroencephalogram, has been implemented in this model. Moreover, the remifentanil concentration in various organs and tissues is predicted, which is a significant improvement with respect to the traditional compartmental models. The availability of the model makes possible the prediction of the effects of remifentanil administration, also accounting for individual parameters.},

keywords = {Modeling, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Cascone2017b,

title = {Mimicking the contractions of a human stomach and their effect on pharmaceuticals},

author = {Sara Cascone and Felice {De Santis} and Gaetano Lamberti},

url = {http://www.sciencedirect.com/science/article/pii/S1773224717305907},

doi = {10.1016/j.jddst.2017.09.008},

issn = {1773-2247},

year  = {2017},

date = {2017-10-01},

journal = {Journal of Drug Delivery Science and Technology},

volume = {41},

pages = {454-461},

abstract = {The prediction of the drug’s fate, once it is released from a pharmaceutical form, is one of the key topic in pharmaceutics and, to evaluate its release kinetics and effectiveness, the reproduction of the mixing conditions experienced by the pharmaceutical system is necessary. In this work a device reproducing the peristaltic waves of the stomach is presented, in order to obtain more reliable drug release profiles. Extended release commercial tablets of diclofenac were tested using both the conventional dissolution method and the new in vitro model proposed. The release profiles obtained using the conventional method and using the artificial stomach were found different both in shape and in magnitude. In particular, a drug concentration gradient along the stomach was realized, reflecting the poor mixing behavior in the model, similarly to what happen in the real physiology. Furthermore, also during the second stage of dissolution the evolutions were different, probably due to the higher shear experienced by the tablet during the first stage in the novel apparatus. The plasma concentration evolutions were predicted by a pharmacokinetic model starting from in vitro dissolution profiles. The comparison of the plasma concentrations confirmed that the dissolution kinetics strongly influences the drug evolution in the human body.},

keywords = {Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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 = {drug release, In silico, In vitro, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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 = {Biodistribution, In vitro, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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 = {In vitro, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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 = {In silico, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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 = {Biodistribution, In silico, Model reduction and lumping, Personalized parameters, Pharmacokinetic models, Pharmacokinetics, Physiologically based modeling, Remifentanil.},

pubstate = {published},

tppubtype = {article}

}

@article{Lamberti2015,

title = {How mathematical modeling tools are helping the pharmaceutical sciences},

author = {Gaetano Lamberti},

url = {http://www.sciencedirect.com/science/article/pii/S0378517315006377},

doi = {10.1016/j.ijpharm.2015.11.003},

issn = {0378-5173},

year  = {2015},

date = {2015-12-30},

journal = {International Journal of Pharmaceutics},

volume = {496},

number = {2},

pages = {157-158},

abstract = {No abstract.},

note = {Editorial},

keywords = {Controlled drug release, Mathematical modeling, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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.},

keywords = {Complexity reduction, In silico, Lumping, Personalization, Pharmacokinetics, Physiologically-Based modeling, Remifentanil},

pubstate = {published},

tppubtype = {article}

}

@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},

number = {2},

pages = {80--97},

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.},

keywords = {In silico, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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.},

keywords = {In silico, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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},

volume = {02},

number = {01},

pages = {e112},

keywords = {In silico, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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 = {Controlled drug release, In vitro, Intestinal Absorption, Mass balance, Oral administration, Pharmacokinetics, Theophylline},

pubstate = {published},

tppubtype = {article}

}

@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.},

keywords = {In silico, in-silico, in-vitro, in-vivo, Pharmacokinetics, testing methods},

pubstate = {published},

tppubtype = {article}

}

@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 = {ADME, Dissolution, Enteric coated, In silico, In vitro, Pharmacokinetic modeling, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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 = {Absorption, Administration, Area Under Curve, Biological, Drug Delivery Systems, Humans, In silico, Models, Oral, Pharmacokinetics, Solubility, Theoretical},

pubstate = {published},

tppubtype = {article}

}

@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 = {In silico, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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.},

keywords = {In silico, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@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},

volume = {48},

number = {6},

pages = {50--53},

keywords = {In silico, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}