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Comprehensive assessment of human pharmacokinetic prediction based on in vivo animal pharmacokinetic data, part 1: Volume of distribution at steady state

Lombardo, Franco and Waters, Nigel and Argikar, Upendra and Dennehy, Michelle and Zhan, Yu and Gunduz, Mithat and Harriman, Shawn and Berellini, Giuliano and Liric Rajlic, Ivana and Obach, R. Scott (2013) Comprehensive assessment of human pharmacokinetic prediction based on in vivo animal pharmacokinetic data, part 1: Volume of distribution at steady state. Journal of Clinical Pharmacology, 53 (2). pp. 167-177. ISSN 0091-2700

Abstract

The authors present a comprehensive analysis on the estimation of volume of distribution at steady state (VDss) in human based on rat, dog, and monkey data on nearly 400 compounds for which there are also associated human data. This data set, to the authors' knowledge, is the largest publicly available, has been carefully compiled from literature reports, and was expanded with some in-house determinations such as plasma protein binding data. This work offers a good statistical basis for the evaluation of applicable prediction methods, their accuracy, and some methods-dependent diagnostic tools. The authors also grouped the compounds according to their charge classes and show the applicability of each method considered to each class, offering further insight into the probability of a successful prediction. Furthermore, they found that the use of fraction unbound in plasma, to obtain unbound volume of distribution, is generally detrimental to accuracy of several methods, and they discuss possible reasons. Overall, the approach using dog and monkey data in the Oie-Tozer equation offers the highest probability of success, with an intrinsic diagnostic tool based on aberrant values (<0 or >1) for the calculated fraction unbound in tissue. Alternatively, methods based on dog data (single-species scaling) and rat and dog data (Oie-Tozer equation with 2 species or multiple regression methods) may be considered reasonable approaches while not requiring data in nonhuman primates. © The Author(s) 2012.

Item Type: Article
Keywords: Allometry Fraction unbound in plasma Fraction unbound in tissues Pharmacokinetics and drug metabolism Scaling Volume of distribution
Date Deposited: 13 Mar 2018 00:45
Last Modified: 25 Jan 2019 00:46
URI: https://oak.novartis.com/id/eprint/5568

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