This Article Full Text (PDF) Other Versions of this Article: AAC.00059-07v1 51/8/2741    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pai, M. P. Articles by Mercier, R.-C. Search for Related Content PubMed PubMed Citation Articles by Pai, M. P. Articles by Mercier, R.-C.

 Previous Article  |  Next Article 

Antimicrob. Agents Chemother. doi:10.1128/AAC.00059-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Influence of morbid obesity on the single dose pharmacokinetics of daptomycin

University of New Mexico Health Sciences Center, College of Pharmacy, School of Medicine, Albuquerque, New Mexico, and University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois

^* To whom correspondence should be addressed. Email: apai{at}salud.unm.edu.

	Abstract

The present study characterized the single dose pharmacokinetics of daptomycin dosed as 4 mg/kg of total body weight (TBW) in seven morbidly obese and seven age, sex, race, and serum creatinine matched healthy subjects. The glomerular filtration rate (GFR) was measured in both groups following a single bolus injection of sodium ¹²⁵I-iothalamate. Noncompartmental analysis was used to determine the pharmacokinetic parameters and these values were normalized against TBW, ideal body weight (IBW), and fat free weight (FFW) for comparison of the two groups. All subjects enrolled in this study were female and the mean ± SD body mass index was 46.2 ± 5.5 and 21.8 ± 1.9 kg/m² for the morbidly obese and normal weight groups, respectively. The C_max and AUC_0-24 values were approximately 60% higher (p<0.05) in morbidly obese compared to the normal weight group and these were a function of the higher total dose received in the morbidly obese group. No differences in daptomycin volume of distribution (Vz), total clearance (CL_T), renal clearance or protein binding was noted between the two groups. TBW provided the best correlation to Vz compared to FFW or IBW. In contrast, TBW overestimated GFR through CL_Cr calculations using the Cockcroft-Gault equation. Use of IBW in the Cockcroft-Gault equation or use of the 4-variable modification of diet in renal disease (MDRD) equation best estimated GFR in morbidly obese subjects. Further studies of daptomycin pharmacokinetics in morbidly obese patients with acute bacterial infections and impaired renal function are necessary to better predict appropriate dosage intervals.

This article has been cited by other articles:

• Seaton, R. A. (2008). Daptomycin: rationale and role in the management of skin and soft tissue infections. J Antimicrob Chemother 62: iii15-iii23 [Abstract] [Full Text]  
• Warren, R. E. (2008). Daptomycin in endocarditis and bacteraemia: a British perspective. J Antimicrob Chemother 62: iii25-iii33 [Abstract] [Full Text]