Details

Autor(en) / Beteiligte

• Knibbe, Catherijne A.J
• Brill, Margreke J.E
• van Rongen, Anne
• Diepstraten, Jeroen
• van der Graaf, Piet Hein
• Danhof, Meindert

Titel

Drug Disposition in Obesity: Toward Evidence-Based Dosing

Ist Teil von

• Annual review of pharmacology and toxicology, 2015-01, Vol.55 (1), p.149-167

Ort / Verlag

United States: Annual Reviews

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.