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 Buelga, D. S.
Right arrow Articles by García, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buelga, D. S.
Right arrow Articles by García, M. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, December 2005, p. 4934-4941, Vol. 49, No. 12
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.12.4934-4941.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Population Pharmacokinetic Analysis of Vancomycin in Patients with Hematological Malignancies

Dolores Santos Buelga,1 María del Mar Fernandez de Gatta,1,{dagger} Emma V. Herrera,2,{dagger} Alfonso Dominguez-Gil,1,3 and María José García1*,{dagger}

Department of Pharmacy and Pharmaceutical Technology, University of Salamanca, Salamanca, Spain,1 Faculty of Chemical Sciences, University of Puebla, Puebla, Mexico,2 Pharmacy Service, University Hospital, Salamanca, Spain3

Received 22 March 2005/ Returned for modification 30 June 2005/ Accepted 27 September 2005

This study determines vancomycin (VAN) population pharmacokinetics (PK) in adult patients with hematological malignancies. VAN serum concentration data (n = 1,004) from therapeutic drug monitoring were collected retrospectively from 215 patients. A one-compartment PK model was selected. VAN pharmacokinetics population parameters were generated using the NONMEM program. A graphic approach and stepwise generalized additive modeling were used to elucidate the preliminary relationships between PK parameters and clinical covariates analyzed. Covariate selection revealed that total body weight (TBW) affected V, whereas renal function, estimated by creatinine clearance, and a diagnosis of acute myeloblastic leukemia (AML) influenced VAN clearance. We propose one general and two AML-specific models. The former was defined by CL (liters/h) = 1.08 x CLCR(Cockcroft and Gault) (liters/h); CVCL = 28.16% and V (liters) = 0.98 x TBW; CVV =37.15%. AML models confirmed this structure but with a higher clearance coefficient (1.17). The a priori performance of the models was evaluated in another 59 patients, and clinical suitability was confirmed. The models were fairly accurate, with more than 33% of the measured concentrations being within ±20% of the predicted value. This therapeutic precision is twofold higher than that of a noncustomized population model (16.1%). The corresponding standardized prediction errors included zero and a standard deviation close to unity. The models could be used to estimate appropriate VAN dosage guidelines, which are not clearly defined for this high-risk population. Their simple structure should allow easy implementation in clinical software and application in dosage individualization using the Bayesian approach.

* Corresponding author. Mailing address: Department of Pharmacy and Pharmaceutical Technology, University of Salamanca, Campus Unamuno, 37001 Salamanca, Spain. Phone: 34 923 294536. Fax: 34 923 294515. E-mail: mjgarcia{at}usal.es.

{dagger} Equal contribution as first author of paper.

Antimicrobial Agents and Chemotherapy, December 2005, p. 4934-4941, Vol. 49, No. 12
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.12.4934-4941.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Thomson, A. H., Staatz, C. E., Tobin, C. M., Gall, M., Lovering, A. M. (2009). Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations. J Antimicrob Chemother 63: 1050-1057 [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»