Prediction of drug concentration-time data in humans from animals: a comparison of three methods

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Iftekhar Mahmood, Kosalaram Goteti

Abstract

The main objective of this work is to evaluate three methods to predict concentration-time data of drugs in humans in a multi-compartment system using animal pharmacokinetic parameters following intravenous administration. The prediction of concentration-time data in humans in a multi-compartment system was based on two proposed methods of Mordenti. The third method was based on the assumption that all drugs follow a single-compartment system. Ten drugs from the literature were chosen that were described by two-compartment model in both human and animals. Two-compartment model parameters (CL, V(c), V(ss), V(β), α, A, β and B) of at least 3 animals were scaled to humans and then were used to predict plasma concentrations-time data in humans. Allometrically scaled pharmacokinetic parameters from animals were also used to predict human profile using one-compartment model as a comparison. The results indicated that in a multi-compartment system, application of pharmacokinetic constants provided better prediction of concentration-time data in humans than the assumption that all drugs follow a single-compartment model. Both the proposed methods of Mordenti provided almost similar concentration-time profiles for most of the drugs. For...Continue Reading

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Citations

Jan 10, 2013·Clinical Pharmacokinetics·Miroslav DostalekManoranjenni Chetty
Feb 9, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Iftekhar Mahmood

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