한국인에서 Vancomycin의 치료적 약물농도 평가

Abstract

Background:We measured plasma vancomycin concentrations as a part of therapeutic drug monitoring (TDM) consultation and compared and analyzed the estimated plasma steady-state therapeutic drug levels of vancomycin obtained on the basis of measured concentrations and by population PK parameters using a PK simulation software in Korean patients to find the factors influencing the discrepancies that lie between these estimates. Materials and Methods:We analyzed the PK parameters of the 188 patients for whom vancomycin TDM was done for 239 episodes between March, 2001 and September, 2002. The trough vancomycin plasma concentrations were measured from plasma samples that were drawn 30 minutes before a vancomycin dose. Based on the measured concentrations, we estimated the steady-state therapeutic levels (ECm) and PK parameters (apparent volumes of distribution, Vdm; clearance, Clm; and half life, T1/2m) using the single-point linear method utilized in CAPCIL (Simkin, Inc.) software program. We compared these with the steady-state levels and PK parameters estimated based on population PK database supplied by the software (ECp, Vdp, Clp, and T1/2p). We stratified and compared the values based on the patients' renal functions, body weights relative to ideal body weights, the magnitude of differences between ECm and ECp. Multiple logistic regression using SAS software package was done to analyze factors that significantly influence the discrepancies. Results:One hundred and eleven were males, and 77 were females. The mean ECm were significantly lower than the mean ECp (11.9±9.9 μg/ml vs. 19.2±19.5 μg/ml). Clm and Vdm were higher than Clp and Vdp, respectively. The same patterns could be applied to the subclasses of patients based on renal functions and body weights. The factors that contribute to the differences in ECm and ECp were body weight, age, height, IBW, BUN, and Clcr, of which age, body weight, and BUN were found to be most significant by multiple regression analysis. Conclusions:Significant sizes of discrepancies between the estimated plasma steady-state therapeutic drug levels of vancomycin obtained on the basis of measured concentrations and by population PK parameters using a PK simulation software in Korean patients necessitate adjustment of dosage and confirmation of steady-state levels by follow-up TDM. We emphasize the need for obtaining vancomycin population PK database in Korean patients.