PMID: 11920753Mar 29, 2002Paper

Drug interactions between HIV protease inhibitors based on physiologically-based pharmacokinetic model

Journal of Pharmaceutical Sciences
Nobuhito ShibataKanji Takada

Abstract

A Physiologically-based pharmacokinetic (PB-PK) model was developed to describe the aspects of pharmacokinetic interactions between five HIV protease inhibitors (ritonavir, amprenavir, nelfinavir, saquinavir, indinavir) in rats. To increase usefulness of this BP-PK model, liver, intestinal tissue and other organ were assumed as compartments in this model. Each compartment was linked with the blood flow and the blood-to-plasma concentration ratios of those drugs, and the absorption process in the intestinal tract was presumed as a first-order kinetics. In addition, this PB-PK model incorporates two elimination processes due to hepatic and intestinal metabolism constructed by in vitro metabolic clearance rates and inhibition constants between HIV protease inhibitors. Excellent agreements were obtained between the predicted and observed concentrations of HIV protease inhibitors in rat plasma after a 20 mg/kg oral dose or co-administration of two kinds of HIV protease inhibitors (amprenavir/indinavir, nelfinavir/amprenavir, saquinavir/amprenavir, amprenavir/ritonavir, indinavir/ritonavir, nelfinavir/ritonavir, and saquinavir/ritonavir) with each 20 mg/kg oral dose. However, underestimates in the predicted plasma concentrations of s...Continue Reading

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Citations

Dec 22, 2005·AIDS Research and Therapy·Han AungChun-Su Yuan
Apr 13, 2007·Expert Opinion on Drug Metabolism & Toxicology·Ivan Nestorov
Nov 2, 2006·Journal of Pharmaceutical Sciences·R Lledó-GarcíaM Merino-Sanjuán
Nov 29, 2008·Toxicology in Vitro : an International Journal Published in Association with BIBRA·N TreijtelA P Freidig
Nov 3, 2007·The Journal of Pharmacy and Pharmacology·Sangeeta MehendaleChun-Su Yuan
Nov 15, 2008·Biopharmaceutics & Drug Disposition·Nobuyuki SugiokaKanji Takada
May 4, 2010·Biopharmaceutics & Drug Disposition·Jianghong FanK Sandy Pang
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Jan 3, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Tjerk BuetersJohan Bylund
Jul 21, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Shinji IwasakiNobuyuki Amano
Oct 26, 2018·Journal of Clinical Pharmacology·Ahizechukwu C EkeUNKNOWN IMPAACT P1026s Protocol Team
Apr 23, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Alison J Parker, J Brian Houston
Oct 28, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·R Lledó-GarcíaM Merino-Sanjuán
Feb 8, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Helen H UsanskyPatrick J Sinko

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