Development and Evaluation of a Novel Software Program, SAKURA-TDM, for Area Under the Concentration-Time Curve-Guided Vancomycin Dosing: A Short Communication.

Abstract

The area under the concentration-time curve (AUC)-guided dosing of vancomycin has been introduced in Japan; however, the optimal dosing method remains controversial. Here, a novel software program was developed for AUC-guided vancomycin dosing and to estimate the theoretical threshold of the steady-state AUC 24 that could reduce the risk of renal injury. A single-center, retrospective, observational study was conducted to develop a novel software program (SAKURA-TDM ver.1.0) for AUC-guided dosing. The estimation accuracy of pharmacokinetic parameters determined using SAKURA-TDM was compared with that of clinically available software programs and assessed with Bland-Altman analysis. In addition, theoretical cutoff points of the steady-state AUC 24 and the predicted trough values were estimated using Youden J statistic approach. The estimation accuracy of pharmacokinetic parameters and AUC determined using SAKURA-TDM was comparable to that of other TDM software programs. Of note, despite a good relationship between the predicted AUC 24 and trough values, the correlation between the predicted AUC 24 and measured trough values was not strong. The cutoff values of the steady-state AUC 24 and the predicted trough value for reducing the probability of a measured trough value of >20 mcg/mL were 513.1 mg·h/L and 15.6 mcg/mL, respectively. We demonstrated the equivalence of the estimated PK parameters between SAKURA-TDM and other TDM software programs available in Japan. Considering the threshold of both trough values and the steady-state AUC and monitoring of the AUC in a non-steady state, it would be possible to reduce the risk of vancomycin-associated renal injury.