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

• Published in: Acta pharmacologica Sinica Vol. 39; no. 2; pp. 286 - 293
• Main Authors: Ji, Xi-wei, Ji, Shuang-min, He, Xiao-rong, Zhu, Xiao, Chen, Rong, Lu, Wei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2018; Nature Publishing Group
• Subjects: Adult; Age; Aged; Aged, 80 and over; Antibiotics; Asian Continental Ancestry Group; Bayes Theorem; Bayesian analysis; Biomedicine; China; Computer simulation; Creatinine; Excretion; Female; Glomerular Filtration Rate; Humans; Immunology; Influence coefficient; Internal Medicine; Kidney - metabolism; Male; Mathematical models; Medical Microbiology; Metabolic Clearance Rate; Middle Aged; Models, Biological; Original; original-article; Pharmacokinetics; Pharmacology/Toxicology; Population; Renal function; Vaccine; Vancomycin; Vancomycin - administration & dosage; Vancomycin - blood; Vancomycin - pharmacokinetics; 万古霉素;描述符;成年;中国;人口;模特儿;肾;模型确认; creatinine; Chinese adult patients; vancomycin; renal function; glomerular filtration rate (GFR); population pharmacokinetics; NONMEM
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2017.57

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 CLc, 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.