JAC Advance Access originally published online on March 19, 2009
Journal of Antimicrobial Chemotherapy 2009 63(5):1050-1057; doi:10.1093/jac/dkp085
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Original research |
Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations
1 Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, UK 2 Pharmacy Department, Western Infirmary, NHS Greater Glasgow and Clyde, Glasgow, Scotland, UK 3 Bristol Centre for Antimicrobial Research and Evaluation, Department of Microbiology, Southmead Hospital, Bristol, UK 4 Pharmacy Department, Southern General Hospital, NHS Greater Glasgow and Clyde, Glasgow, Scotland, UK
Received 1 October 2008; returned 7 December 2008; revised 2 February 2009; accepted 20 February 2009
* Corresponding author. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G40NR, Scotland, UK. Tel: +44-141-548-2506; Fax: +44-141-552-2562; E-mail: alison.h.thomson{at}strath.ac.uk
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.
Keywords: population pharmacokinetics , therapeutic drug monitoring , antimicrobial agents
Present address: School of Pharmacy, University of Queensland, Brisbane, Qld 4072, Australia.