The influencing factors of pharmacokinetics of Vancomycin and its trough concentration in patients with augmented renal clearance

Abstract

Objective To observe the characteristics of pharmacokinetics of Vancomycin and its serum trough concentration in patients with augmented renal clearance (ARC), and to analyze the influencing factors of trough concentration of Vancomycin. Methods A retrospective analysis was conducted in steady-state trough concentrations of Vancomycin in adult patients of Suzhou Municipal Hospital from July 2013 to July 2017. According to the estimated glomerular filtration rate (eGFR), the patients were divided into the ARC group [eGFR >130 ml/(min•1.73 m2)] and the normal renal function group [eGFR = 50-130 ml/(min•1.73 m2)]. The pharmacokinetic parameters of Vancomycin were calculated by Bayesian feedback method. The influencing factors of Vancomycin were analyzed by univariate and multivariate factors Logistic regression analysis. Results There were 291 patients who were collected trough concentrations of Vancomycin including 78 patients in the ARC group and 213 patients in the normal renal function group. In the ARC group, the average daily dose of Vancomycin was much higher than that in the normal renal function group [(2 150±550)mg vs. (1 812±453)mg, P = 0.000], but the average trough concentration was much lower than that in the normal renal function group [(8.3±6.4)mg/L vs. (13.6±7.2)mg/L, P = 0.000]. Only 16.7% of the ARC patients had the trough concentrations of Vancomycin in the target range (10-20 mg/L). Comparing with the normal renal function group, the difference was significant (16.7% vs. 46.5%, P = 0.000). According to the pharmacokinetic parameters by Bayesian feedback method, the apparent volume of distribution (Vd) was significantly increased in the ARC group than the normal renal function group [(69.3±27.7)L vs. (60.5±21.3)L, P = 0.000], and clearance rate (CL) was significantly increased in the ARC group [(7.0±0.9) L/h vs. (4.3±0.4) L/h, P = 0.000]. Logistic regression analysis showed that the age, body weight, and the serum creatinine before administration were the independent factors of low trough concentration of Vancomycin. Conclusions The serum trough concentration of Vancomycin is significantly reduced in the ARC patients. The pharmacokinetic parameters in the ARC patients are significantly different from those with normal renal function. The age, body weight, and the serum creatinine before administration have more influences on the trough concentration of Vancomycin. Key words: Augmented renal clearance; Vancomycin; Trough concentration; Pharmacokinetics; Influence factors