Article

Influences of renal function descriptors on population pharmacokinetic modeling of vancomycin in Chinese adult patients

Authors: Xi-wei JI1, Shuang-min JI2, Xiao-rong HE3, Xiao ZHU4, Rong CHEN5, Wei LU5
1 Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China
2 Center for Drug Evaluation, China Food and Drug Administration, Beijing 100038, China
3 Department of Pharmacy, Beijing Hospital, Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Beijing 100730, China
4 School of Pharmacy, University of Otago, Dunedin, New Zealand
5 Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Corresponding to: Wei LU: luwei_pk@hsc.pku.edu.cn,
DOI: 10.1038/aps.2017.57
Received: 20 December 2016
Accepted: 19 April 2017
Advance online: 24 August 2017

Abstract

Abstract
Vancomycin, a glycopeptide antibiotic for the treatment of grampositive infections, is mainly eliminated via glomerular filtration. Thus, its therapeutic effects are affected predominantly by renal function. The aim of this study was to develop a population pharmacokinetic model of vancomycin for Chinese adult patients and to investigate the influence of different renal function descriptors on the predictability of the model. A retrospective analysis was performed based on the blood concentrations of vancomycin in 218 Chinese adult patients. Among these patients, the data from 160 were used to establish the population pharmacokinetic model, and the data from the remaining 58 patients were used for external model validation. A simulation was employed to determine the appropriate initial vancomycin dosage regimens in adult Chinese patients for reaching the target steady-state trough concentrations of 10–15 mg/L and 15–20 mg/L. We developed a one-compartment model with first-order absorption to characterize the concentration-time profile of vancomycin. There was a positive correlation between the body clearance of vancomycin and renal function; both creatinine clearance (CLCr) and age were the covariates that influenced the PK of vancomycin, and the excretion of vancomycin decreased as renal function diminishing with age. The typical clearance (CL) value was 2.829 L/h for 75-year-old patients with CLCr values of 80 mL/min, and the rate constant of CL with the CLCr changing at 1 mL/min was 0.00842. The influence coefficient of age on CL was 0.08143. The external validation results revealed that the current different descriptors of renal function behaved similarly to the predicted performance of the models. In conclusion, the developed model is appropriate for Bayesian dose predictions of vancomycin concentrations in the population of Chinese adult patients. Furthermore, the simulation provides a reference for clinical optimized antibacterial therapy with vancomycin.
Keywords: vancomycin; population pharmacokinetics; Chinese adult patients; renal function; creatinine; glomerular filtration rate (GFR); NONMEM

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