PRIN 2010-11

@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{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}

}