title: Drug disposition in obesity: toward evidence-based dosing.
abstract: Obesity and morbid obesity are associated with many physiological changes affecting pharmacokinetics, such as increased blood volume, cardiac output, splanchnic blood flow, and hepatic blood flow. In obesity, drug absorption appears unaltered, although recent evidence suggests that this conclusion may be premature. Volume of distribution may vary largely, but the magnitude and direction of changes seem difficult to predict, with extrapolation on the basis of total body weight being the best approach to date. Changes in clearance may be smaller than in distribution, whereas there is growing evidence that the influence of obesity on clearance can be predicted on the basis of reported changes in the metabolic or elimination pathways involved. For obese children, we propose two methods to distinguish between developmental and obesity-related changes. Future research should focus on the characterization of physiological concepts to predict the optimal dose for each drug in the obese population.
authors.affiliation: Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands; email: c.knibbe@antoniusziekenhuis.nl.
authors.forename: Catherijne A J
authors.initials: CA
authors.lastname: Knibbe
authors.forename: Margreke J E
authors.initials: MJ
authors.lastname: Brill
authors.forename: Anne
authors.initials: A
authors.lastname: van Rongen
authors.forename: Jeroen
authors.initials: J
authors.lastname: Diepstraten
authors.forename: Piet Hein
authors.initials: PH
authors.lastname: van der Graaf
authors.forename: Meindert
authors.initials: M
authors.lastname: Danhof
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D001682:Biological Availability; D015992:Body Mass Index; D001835:Body Weight; D002648:Child; D054796:Drug Dosage Calculations; D019317:Evidence-Based Medicine / Q000379:methods*; D005260:Female; D065569:Gastrointestinal Absorption; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010599:Pharmacokinetics; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D004364:Pharmaceutical Preparations
keywords: childhood; children; morbidly obese; obese; pharmacodynamics; pharmacokinetics; precision medicine; prediction in pharmacology