Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations

Thomson, A. H., Staatz, C. E., Tobin, C. M., Gall, M. and Lovering, A. M. (2009) Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations. Journal of Antimicrobial Chemotherapy, 63 5: 1050-1057. doi:10.1093/jac/dkp085

Author Thomson, A. H.
Staatz, C. E.
Tobin, C. M.
Gall, M.
Lovering, A. M.
Title Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations
Journal name Journal of Antimicrobial Chemotherapy   Check publisher's open access policy
ISSN 0305-7453
Publication date 2009-01-01
Year available 2009
Sub-type Article (original research)
DOI 10.1093/jac/dkp085
Open Access Status
Volume 63
Issue 5
Start page 1050
End page 1057
Total pages 8
Editor Johnson, A. P.
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject C1
111502 Clinical Pharmacology and Therapeutics
920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified
Formatted abstract
Objectives: The aims of this study were to develop a population pharmacokinetic model of vancomycin in adult patients, to use this model to develop dosage guidelines targeting vancomycin trough concentrations of 10–15 mg/L and to evaluate the performance of these new guidelines.
Methods: All data analyses were performed using NONMEM®. A population pharmacokinetic model was first developed from vancomycin dosage and concentration data collected during routine therapeutic drug monitoring in 398 patients, then new vancomycin dosage guidelines were devised by using the model to predict vancomycin trough concentrations in a simulated dataset. Individual estimates of CL and V1 were then obtained in an independent group of 100 patients using the population model and the POSTHOC option. These individual estimates were used to predict vancomycin trough concentrations and steady-state AUC24/MIC ratios using the current and new dosage guidelines.
Results: The population analysis found that the vancomycin data were best described using a bi-exponential elimination model with a typical CL of 3.0 L/h that changed by 15.4% for every 10 mL/min difference from a CLCR of 66 mL/min. Vss was 1.4 L/kg. The proposed dosage guidelines were predicted to achieve 55% of vancomycin troughs within 10–15 mg/L and 71% within 10–20 mg/L, which is significantly higher than current guidelines (19% and 22%, respectively). The proportion of AUC24/MIC ratios above 400 was also higher, 87% compared with 58%.
Conclusions: New vancomycin dosage guidelines have been developed that achieve trough concentrations of 10–15 mg/L earlier and more consistently than current guidelines.
Keyword Population pharmacokinetics
Therapeutic drug monitoring
Antimicrobial agents
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 37 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 13 Jul 2009, 22:49:15 EST by Charna Kovacevic on behalf of School of Pharmacy