The effects of obesity on drug pharmacokinetics in humans

• Published in: Expert opinion on drug metabolism & toxicology Vol. 7; no. 6; p. 697
• Main Authors: Morrish, Glynn A, Pai, Manjunath P, Green, Bruce
• Format: Journal Article
• Language: English
• Published: England 01.06.2011
• Subjects: Body Composition; Body Mass Index; Body Weight; Dose-Response Relationship, Drug; Female; Humans; Male; Obesity - metabolism; Organ Size; Pharmaceutical Preparations - metabolism; Pharmacokinetics; Physiological Phenomena
• ISSN: 1744-7607
• DOI: 10.1517/17425255.2011.570331

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. 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. 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.