5 (193) In stock
This study was conducted to comprehensively survey the available literature on intravenous pharmacokinetic parameters in the rat, dog, monkey, and human, and to compare common methods for extrapolation of clearance, to identify the most appropriate species to use in pharmacokinetic lead optimization, and to ascertain whether adequate prospective measures of predictive success are currently available. One hundred three nonpeptide xenobiotics were identified with intravenous pharmacokinetic data in rat, dog, monkey, and human; both body weight- and hepatic blood flow-based methods were used for scaling of clearance. Allometric scaling approaches, particularly those using data from only two of the preclinical species, were less successful at predicting human clearance than methods based on clearance as a set fraction of liver blood flow from an individual species. Furthermore, commonly used prospective measures of allometric scaling success, including correlation coefficient and allometric exponent, failed to discriminate between successful and failed allometric predictions. In all instances, the monkey tended to provide the most qualitatively and quantitatively accurate predictions of human clearance and also afforded the least biased predictions compared with other species. Additionally, the availability of data from both common nonrodent species (dog and monkey) did not ensure enhanced predictive quality compared with having only monkey data. The observations in this investigation have major implications for pharmacokinetic lead optimization and for prediction of human clearance from in vivo preclinical data and support the continued use of nonhuman primates in preclinical pharmacokinetics.
The Use of the African Green Monkey as a Preclinical Model for Ocular Pharmacokinetic Studies
Humans are animals, but are animals human enough? A systematic review and meta-analysis on interspecies differences in renal drug clearance - ScienceDirect
Utility of a single adjusting compartment: a novel methodology for whole body physiologically-based pharmacokinetic modelling, Theoretical Biology and Medical Modelling
The TeGenero Incident and the Duff Report Conclusions: A Series of Unfortunate Events or an Avoidable Event? - Christopher J. Horvath, Mark N. Milton, 2009
Molecules, Free Full-Text
Assessment of drug metabolism enzyme and transporter pharmacogenetics in drug discovery and early development: perspectives of the I-PWG
Quantitative Assessment of Blood Lactate in Shock: Measure of Hypoxia or Beneficial Energy Source
Comprehensive Assessment of Human Pharmacokinetic Prediction Based on In Vivo Animal Pharmacokinetic Data, Part 1: Volume of Distribution at Steady State - Lombardo - 2013 - The Journal of Clinical Pharmacology - Wiley Online Library
Brian R Smith's research works GlaxoSmithKline, London (GSK) and other places
IJMS, Free Full-Text
PDF) PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 2: Comparative assessment of prediction methods of human volume of distribution
IJMS, Free Full-Text
Full article: Species differences in the pharmacokinetics and metabolism of reparixin in rat and dog
