This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ASM journals
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pai, M. P.
Right arrow Articles by Mercier, R.-C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pai, M. P.
Right arrow Articles by Mercier, R.-C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2007, p. 2741-2747, Vol. 51, No. 8
0066-4804/07/$08.00+0     doi:10.1128/AAC.00059-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Influence of Morbid Obesity on the Single-Dose Pharmacokinetics of Daptomycin{triangledown}

Manjunath P. Pai,1* Jeffrey P. Norenberg,1 Tamara Anderson,1 Diane W. Goade,2 Keith A. Rodvold,3 Robert A. Telepak,2 and Renee-Claude Mercier1,2

College of Pharmacy,1 School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico,2 University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois3

Received 15 January 2007/ Returned for modification 27 April 2007/ Accepted 27 May 2007

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 for both groups following a single bolus injection of [125I]sodium 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 (±standard deviation) body mass index was 46.2 ± 5.5 kg/m2 or 21.8 ± 1.9 kg/m2 for the morbidly obese or normal-weight group, respectively. The maximum plasma concentration and area under the concentration-time curve from dosing to 24 h were approximately 60% higher (P < 0.05) in the morbidly obese group than in 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 (V), total clearance, renal clearance, or protein binding were noted between the two groups. Of TBW, FFW, or IBW, TBW provided the best correlation to V. In contrast, TBW overestimated GFR through creatinine clearance calculations using the Cockcroft-Gault equation. Use of IBW in the Cockcroft-Gault equation or use of the four-variable modification of diet in renal disease 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.

* Corresponding author. Mailing address: College of Pharmacy, MSC09 5360, 1 University of New Mexico, Albuquerque, NM 87131-0001. Phone: (505) 272-8931. Fax: (505) 272-6749. E-mail: apai{at}salud.unm.edu

{triangledown} Published ahead of print on 4 June 2007.

Antimicrobial Agents and Chemotherapy, August 2007, p. 2741-2747, Vol. 51, No. 8
0066-4804/07/$08.00+0     doi:10.1128/AAC.00059-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bubalo, J. S., Munar, M. Y., Cherala, G., Hayes-Lattin, B., Maziarz, R. (2009). Daptomycin Pharmacokinetics in Adult Oncology Patients with Neutropenic Fever. Antimicrob. Agents Chemother. 53: 428-434 [Abstract] [Full Text]  
  • 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]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»