The Constraints, Construction, and Verification of a Strain-Specific Physiologically Based Pharmacokinetic Rat Model

Journal of Pharmaceutical Sciences
Helen MustherMasoud Jamei

Abstract

The use of in vitro-in vivo extrapolation (IVIVE) techniques, mechanistically incorporated within physiologically based pharmacokinetic (PBPK) models, can harness in vitro drug data and enhance understanding of in vivo pharmacokinetics. This study's objective was to develop a user-friendly rat (250 g, male Sprague-Dawley) IVIVE-linked PBPK model. A 13-compartment PBPK model including mechanistic absorption models was developed, with required system data (anatomical, physiological, and relevant IVIVE scaling factors) collated from literature and analyzed. Overall, 178 system parameter values for the model are provided. This study also highlights gaps in available system data required for strain-specific rat PBPK model development. The model's functionality and performance were assessed using previous literature-sourced in vitro properties for diazepam, metoprolol, and midazolam. The results of simulations were compared against observed pharmacokinetic rat data. Predicted and observed concentration profiles in 10 tissues for diazepam after a single intravenous (i.v.) dose making use of either observed i.v. clearance (CLiv) or in vitro hepatocyte intrinsic clearance (CLint) for simulations generally led to good predictions in vari...Continue Reading

References

Feb 1, 1991·Journal of Pharmacokinetics and Biopharmaceutics·A Bernareggi, M Rowland
Dec 1, 1989·Alimentary Pharmacology & Therapeutics·J FallingborgH H Rasmussen
Oct 2, 1967·Biochimica Et Biophysica Acta·G J Nelson
Jun 1, 1984·Journal of Pharmaceutical Sciences·Y IgariM Hanano
Oct 1, 1994·Journal of Pharmacokinetics and Biopharmaceutics·R KawaiM Rowland
Jul 1, 1993·Pharmaceutical Research·B Davies, T Morris
Sep 1, 1995·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·K ZomorodiJ B Houston
Jan 10, 2002·Journal of Pharmaceutical Sciences·Patrick Poulin, Frank-Peter Theil
Aug 17, 2002·The Journal of Pharmacology and Experimental Therapeutics·Tsutomu KotegawaDavid J Greenblatt
May 5, 2004·Journal of Pharmaceutical Sciences·Leonid M Berezhkovskiy
Aug 21, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hannah M Jones, J Brian Houston
Mar 21, 2007·Pharmaceutical Research·Trudy Rodgers, Malcolm Rowland
Jul 11, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stefan S De BuckRon A H J Gilissen
Nov 6, 2007·Current Drug Metabolism·Jiansong YangAmin Rostami-Hodjegan
Dec 22, 2007·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Helen GarsideMichael Sullivan
Mar 12, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Doreen MitschkeUrsula Moenning
Feb 10, 2009·Expert Opinion on Drug Metabolism & Toxicology·Masoud JameiAmin Rostami-Hodjegan
Apr 22, 2009·The AAPS Journal·Masoud JameiGeoffrey Tucker
Oct 3, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Loren M BerryMin-Hwa Jasmine Lin
Apr 8, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Makoto AokiMasahiro Hayashi
Sep 22, 2010·Annual Review of Pharmacology and Toxicology·Malcolm RowlandGeoffrey Tucker
Mar 31, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Angus N R NeddermanDavid Higton
May 6, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Peter J BungayNatalie M Mount
Jul 6, 2011·Critical Reviews in Toxicology·Robert A Roth, Patricia E Ganey
Nov 1, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Hannah M JonesIain B Gardner

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