Prospective evaluation of vancomycin pharmacokinetics in a heterogeneous critically ill population

Rich pharmacokinetic data on vancomycin in critically ill patients are lacking. The purpose of this study was to evaluate the pharmacokinetics of vancomycin in this population using rich pharmacokinetic sampling. Nineteen critically ill patients received individualized vancomycin doses by intermittent infusion to achieve target trough concentrations (15-20 mg/L). Blood samples were collected following the third or later dose of vancomycin. Serial blood samples were collected at 30 min following initiation of the vancomycin infusion; at the end of the infusion; serially at 60, 120, 300, and 480 min after the infusion finished; and immediately prior to the next dose. Vancomycin concentration-time profiles at steady state were fit to a noncompartmental model to determine the pharmacokinetic parameters. Vancomycin trough concentration was correlated to AUC_0-24 (r = 0.83, P < 0.001). Total body weight was a predictor of volume of distribution (r = 0.43, P = 0.03). Age, serum creatinine, and creatinine clearance (CrCl) were found to be predictors for vancomycin clearance (r = -0.67, -0.52, and, 0.72, respectively). CrCl was the best predictor of vancomycin systemic clearance, and addition of other variables to a multivariate model failed to improve model fit. Vancomycin trough concentration may not be an adequate surrogate of AUC_0-24. Additional research is needed to determine dosing strategies to optimize AUC_0-24 while limiting toxicity.