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
Services
Right arrow Similar articles in this journal
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 Dvorchik, B.
Right arrow Articles by Kastrissios, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dvorchik, B.
Right arrow Articles by Kastrissios, H.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2004, p. 2799-2807, Vol. 48, No. 8
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.8.2799-2807.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Population Pharmacokinetics of Daptomycin

Barry Dvorchik,1* Robert D. Arbeit,1,{dagger} Julia Chung,2 Susan Liu,2 William Knebel,2 and Helen Kastrissios2

Cubist Pharmaceuticals, Inc., Lexington, Massachusetts 02421,1 GloboMax Holdings LLC, Hanover, Maryland 210762

Received 9 November 2003/ Returned for modification 26 January 2004/ Accepted 4 April 2004

Data from subjects in nine phase 1 (n = 153) and six phase 2/3 (n = 129) clinical trials were combined to identify factors contributing to interindividual variability in daptomycin pharmacokinetics (PK). Over 30 covariates were considered. A two-compartment model with first-order elimination provided the best fit for data on daptomycin concentrations in plasma over time. In the final population PK model, daptomycin plasma clearance (CL) was a function of renal function, body temperature, and sex. Of these factors, renal function contributed most significantly to interindividual variability. CL varied linearly with the estimated creatinine clearance. CL among dialysis subjects was approximately one-third that of healthy subjects (0.27 versus 0.81 liter/h). CL in females was 80% that in males; however, in clinical trials, the outcome was not affected by sex and therefore this effect is not considered clinically meaningful. The relationship with body temperature should be interpreted cautiously since the analysis included only a limited number of subjects who were hyperthermic. The volume of distribution of the peripheral compartment (V2) and intercompartmental clearance (Q) were linearly related to body weight. V2 increased approximately twofold in the presence of an acute infection. No factors were identified that significantly impacted V1. This analysis supports the dosing of daptomycin on a milligram-per-kilogram-of-body-weight basis and suggests that modified dosing regimens are indicated for patients with severe renal disease and for those undergoing dialysis.

* Corresponding author. Present address: Barry Dvorchik & Associates, Inc., 5809 Piney Lane Dr., Suite 105, Tampa, FL 33625. Phone: (813) 951-2789. Fax: (832) 213-2008. E-mail: bdvorchi{at}tampabay.rr.com.

{dagger} Present address: Paratek Pharmaceuticals, Boston, MA 02111.

Antimicrobial Agents and Chemotherapy, August 2004, p. 2799-2807, Vol. 48, No. 8
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.8.2799-2807.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bowker, K. E., Noel, A. R., MacGowan, A. P. (2009). Comparative antibacterial effects of daptomycin, vancomycin and teicoplanin studied in an in vitro pharmacokinetic model of infection. J Antimicrob Chemother 64: 1044-1051 [Abstract] [Full Text]  
  • Chakraborty, A., Roy, S., Loeffler, J., Chaves, R. L. (2009). Comparison of the pharmacokinetics, safety and tolerability of daptomycin in healthy adult volunteers following intravenous administration by 30 min infusion or 2 min injection. J Antimicrob Chemother 64: 151-158 [Abstract] [Full Text]  
  • Salama, N. N., Segal, J. H., Churchwell, M. D., Patel, J. H., Gao, L., Heung, M., Mueller, B. A. (2009). Intradialytic Administration of Daptomycin in End Stage Renal Disease Patients on Hemodialysis. CJASN 4: 1190-1194 [Abstract] [Full Text]  
  • 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]  
  • Hawkey, P. M. (2008). Pre-clinical experience with daptomycin. J Antimicrob Chemother 62: iii7-iii14 [Abstract] [Full Text]  
  • Ponticelli, C. (2008). New recommendations in the treatment of Gram-positive bacteraemia in dialysis patients. Nephrol Dial Transplant 23: 27-32 [Full Text]  
  • Burkhardt, O., Joukhadar, C., Traunmuller, F., Hadem, J., Welte, T., Kielstein, J. T. (2008). Elimination of daptomycin in a patient with acute renal failure undergoing extended daily dialysis. J Antimicrob Chemother 61: 224-225 [Full Text]  
  • Pai, M. P., Norenberg, J. P., Anderson, T., Goade, D. W., Rodvold, K. A., Telepak, R. A., Mercier, R.-C. (2007). Influence of Morbid Obesity on the Single-Dose Pharmacokinetics of Daptomycin. Antimicrob. Agents Chemother. 51: 2741-2747 [Abstract] [Full Text]  
  • Vouillamoz, J., Moreillon, P., Giddey, M., Entenza, J. M. (2006). Efficacy of daptomycin in the treatment of experimental endocarditis due to susceptible and multidrug-resistant enterococci. J Antimicrob Chemother 58: 1208-1214 [Abstract] [Full Text]  
  • Pai, M. P, Mercier, R.-C., Allen, S. E (2006). Using Vancomycin Concentrations for Dosing Daptomycin in a Morbidly Obese Patient with Renal Insufficiency. The Annals of Pharmacotherapy 40: 553-558 [Abstract] [Full Text]  
  • Huang, V., Rybak, M. J. (2006). Evaluation of daptomycin activity against Staphylococcus aureus in an in vitro pharmacodynamic model under normal and simulated impaired renal function. J Antimicrob Chemother 57: 116-121 [Abstract] [Full Text]  
  • Schriever, C. A., Fernandez, C., Rodvold, K. A., Danziger, L. H. (2005). Daptomycin: A novel cyclic lipopeptide antimicrobial. Am J Health Syst Pharm 62: 1145-1158 [Abstract] [Full Text]  
  • Dvorchik, B. H., Damphousse, D. (2005). The Pharmacokinetics of Daptomycin in Moderately Obese, Morbidly Obese, and Matched Nonobese Subjects. J Clin Pharmacol 45: 48-56 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»