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Medline ® Abstract for Reference 58

of 'Dosing of anticancer agents in adults'

The effects of obesity on drug pharmacokinetics in humans.
Morrish GA, Pai MP, Green B
Expert Opin Drug Metab Toxicol. 2011 Jun;7(6):697-706. Epub 2011 Mar 22.
INTRODUCTION: The prevalence of obesity and associated co-morbid conditions is increasing globally. Physiological changes accompanying obesity are likely to result in altered drug pharmacokinetics; however, there is paucity of information on how to best dose adjust for the obese.
AREAS COVERED: This review presents material describing physiological changes that occur in the obese and their relationship to body composition. The review also discusses various dosing metrics currently used to scale for size, and relationships between body composition and pharmacokinetic parameters. Through this, the reader is provided with a greater understanding of the key concepts regarding the physiological changes associated with obesity and how they relate to the changes in the pharmacokinetics.
EXPERT OPINION: There is a nonlinear relationship between total body weight and the physiological variables that determine drug clearance. Metrics that describe pharmacokinetics at the extremes of weight in a semi-mechanistic manner should be used as drug dosing scalars, with clinical trials adequately designed to correctly identify the most appropriate dosing scalar.
Model Answers Pty Ltd, Brisbane, Australia. glynn.morrish@gmail.com