Investigation of the age dependency of vancomycin clearance by population pharmacokinetic modeling.

PURPOSE

The aim of this study was to evaluate the influence of age and other possible covariates on vancomycin clearance in order to define a possible cut off value of age for dose optimization in elderly patients from data obtained during therapeutic drug monitoring.

MATERIALS AND METHODS

Population pharmacokinetic analysis of 256 samples obtained from 144 patients was performed by using NONMEM. A one-compartment model was applied as the base model with first-order conditional estimation method with interaction (FOCE-I). The influence of different covariates was investigated by stepwise covariate modeling, and the final model was evaluated by goodness-of-fit plots and bootstrap analysis using 1,000 datasets.

RESULTS

In the final model, the mean values for vancomycin clearance (CL) and volume of distribution (V) were 2.32 L/h and 19.2 L, respectively. Vancomycin CL was significantly influenced by creatinine CL (CL) in a stepwise covariate modeling, and it was lowest in patients of 75 years and above when compared with other age groups.

CONCLUSION: Vancomycin CL decreases progressively with increasing age due to the reduction in CL in older patients. Therefore, dose adjustment should be based on CL for safe use of vancomycin in patients ≥ 75 years of age or older.
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