Presented in part at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, Illinois, September 17–20, 2011.
Reviews of Therapeutics
Drug Dosing Based on Weight and Body Surface Area: Mathematical Assumptions and Limitations in Obese Adults
Article first published online: 18 JUN 2012
© 2012 Pharmacotherapy Publications, Inc. All rights reserved.
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Volume 32, Issue 9, pages 856–868, September 2012
How to Cite
Pharmacotherapy 2012; 32(9): 856–868
- Issue published online: 4 SEP 2012
- Article first published online: 18 JUN 2012
- body surface area;
- fat free
The average weight of adults in the United States has increased by 25 pounds (11 kg) over the past 50 years, with a marginal change in height. Drugs are generally dosed according to one of three approaches: fixed dosing, weight-based dosing, or body surface area–based dosing. Dosing based on body weight or body surface area assumes that drug pharmacokinetic parameters increase in proportion with increasing body size. In contrast, dosing drugs on a fixed basis assumes that drug pharmacokinetic parameters do not increase with body size. Unfortunately, early stages of clinical drug development tend to include adults within a narrow range of body size. This study population does not reflect the current U.S. population distribution and does not permit evaluation of the correct relationship between body size and drug clearance. As a consequence, a weight-based or body surface area–based dosing regimen defined during drug development may not be applicable to U.S. patient populations. These dosing strategies are more likely to result in drug overexposure (weight-based approach) or underexposure (body surface area–based approach) among obese patients. Alternate weight descriptors such as ideal body weight, adjusted body weight, fat-free weight, and lean body weight are used to prevent drug overexposure with weight-based dosing, but their benefits and limitations must be understood. Reappraisal of the drug dosing paradigm is needed in this era of rising obesity; however, until drug-specific reviews can be performed, clinical studies must include patients at the extremes of the weight continuum to ensure applicable dose extrapolation for body size.