Underestimation of the Calculated Area Under the Concentration-Time Curve Based on Serum Creatinine for Vancomycin Dosing

BACKGROUND: The ratio of the steady-state 24-hour area under the concentration-time curve (ssAUC(24)) to the MIC (AUC(24)/MIC) for vancomycin has been recommended as the preferred pharmacodynamic index. The aim of this study was to assess whether the calculated AUC(24) (cAUC(24)) using the creatinine clearance (CLcr) differs from the ssAUC(24) based on the individual pharmacokinetic data estimated by a commercial software. MATERIALS AND METHODS: The cAUC(24) was compared with the ssAUC(24) with respect to age, body mass index, and trough concentration of vancomycin and the results were expressed as median and interquartile ranges. A correlation between the cAUC(24) and ssAUC(24) and the trough concentration of vancomycin was evaluated. The probability of reaching an AUC(24)/MIC of 400 or higher was compared between the cAUC(24) and ssAUC(24) for different MICs of vancomycin and different daily doses by simulation in a subgroup with a trough concentration of 10 mg/L and higher. RESULTS: The cAUC(24) was significantly lower than the ssAUC(24) (392.38 vs. 418.32 mg·hr/L, P < 0.0001) and correlated weakly with the trough concentration (r = 0.649 vs. r = 0.964). Assuming a MIC of 1.0 mg/L, the probability of reaching the value of 400 or higher was 77.5% for the cAUC(24)/MIC and 100% for the ssAUC(24)/MIC in patients with a trough concentration of 10 mg/L and higher. If the MIC increased to 2.0 mg/L, the probability was 57.7% for the cAUC(24)/MIC and 71.8% for the ssAUC(24)/MIC at a daily vancomycin dose of 4,000 mg. CONCLUSIONS: The cAUC(24) using the calculated CLcr is usually underestimated compared with the ssAUC(24) based on individual pharmacokinetic data. Therefore, to obtain a more accurate AUC(24), therapeutic monitoring of vancomycin rather than a simple calculation based on the CLcr should be performed, and a more accurate biomarker for renal function is needed.