Underestimation of the Calculated Area Under the Concentration-Time Curve Based on Serum Creatinine for Vancomycin Dosing
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Background: The ratio of the steady-state 24-hour area under the concentration-time curve (ssAUC24) to the MIC (AUC24/MIC) forvancomycin has been recommended as the preferred pharmacodynamic index. The aim of this study was to assess whether thecalculated AUC24 (cAUC24) using the creatinine clearance (CLcr) differs from the ssAUC24 based on the individual pharmacokineticdata estimated by a commercial software. Materials and Methods: The cAUC24 was compared with the ssAUC24 with respect to age, body mass index, and trough concentrationof vancomycin and the results were expressed as median and interquartile ranges. A correlation between the cAUC24 andssAUC24 and the trough concentration of vancomycin was evaluated. The probability of reaching an AUC24/MIC of 400 or higherwas compared between the cAUC24 and ssAUC24 for different MICs of vancomycin and different daily doses by simulation in asubgroup with a trough concentration of 10 mg/L and higher. Results: The cAUC24 was significantly lower than the ssAUC24 (392.38 vs. 418.32 mg·hr/L, P < 0.0001) and correlated weakly withthe 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 orhigher was 77.5% for the cAUC24/MIC and 100% for the ssAUC24/MIC in patients with a trough concentration of 10 mg/L andhigher. If the MIC increased to 2.0 mg/L, the probability was 57.7% for the cAUC24/MIC and 71.8% for the ssAUC24/MIC at a dailyvancomycin dose of 4,000 mg. Conclusions: The cAUC24 using the calculated CLcr is usually underestimated compared with the ssAUC24 based on individualpharmacokinetic data. Therefore, to obtain a more accurate AUC24, therapeutic monitoring of vancomycin rather than a simplecalculation based on the CLcr should be performed, and a more accurate biomarker for renal function is needed.
Abstract
Background: The ratio of the steady-state 24-hour area under the concentration-time curve (ssAUC24) to the MIC (AUC24/MIC) forvancomycin has been recommended as the preferred pharmacodynamic index. The aim of this study was to assess whether thecalculated AUC24 (cAUC24) using the creatinine clearance (CLcr) differs from the ssAUC24 based on the individual pharmacokineticdata estimated by a commercial software. Materials and Methods: The cAUC24 was compared with the ssAUC24 with respect to age, body mass index, and trough concentrationof vancomycin and the results were expressed as median and interquartile ranges. A correlation between the cAUC24 andssAUC24 and the trough concentration of vancomycin was evaluated. The probability of reaching an AUC24/MIC of 400 or higherwas compared between the cAUC24 and ssAUC24 for different MICs of vancomycin and different daily doses by simulation in asubgroup with a trough concentration of 10 mg/L and higher. Results: The cAUC24 was significantly lower than the ssAUC24 (392.38 vs. 418.32 mg·hr/L, P < 0.0001) and correlated weakly withthe 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 orhigher was 77.5% for the cAUC24/MIC and 100% for the ssAUC24/MIC in patients with a trough concentration of 10 mg/L andhigher. If the MIC increased to 2.0 mg/L, the probability was 57.7% for the cAUC24/MIC and 71.8% for the ssAUC24/MIC at a dailyvancomycin dose of 4,000 mg. Conclusions: The cAUC24 using the calculated CLcr is usually underestimated compared with the ssAUC24 based on individualpharmacokinetic data. Therefore, to obtain a more accurate AUC24, therapeutic monitoring of vancomycin rather than a simplecalculation based on the CLcr should be performed, and a more accurate biomarker for renal function is needed.
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