title: Initial dosage regimens of vancomycin for Chinese adult patients based on population pharmacokinetic analysis.
abstract: OBJECTIVE
  To build a population pharmacokinetic model for Chinese adult patients and develop initial dosage regimens for patients with different degrees of renal function to achieve target steady-state trough concentrations in the range of 10 - 15 and 15 - 20 mg/l.
  
  
  METHODS
  Data on serum vancomycin concentration was collected from a retrospective study including 72 Chinese adult patients. NONMEM was used to build the population pharmacokinetic model, and a one-compartment model was chosen to describe the vancomycin concentration-time profile. Internal evaluation by bootstrap and visual predictive check (VPC) was performed to evaluate the robustness and prediction of the final model. Monte Carlo simulations were conducted to develop initial dosage regimens to achieve target trough concentrations.
  
  
  RESULTS
  A one-compartment model was built with creatinine clearance (CLcr) as the key covariate influencing drug clearance. The estimated drug clearance for patients with normal renal function (CLcr ≥ 80 ml/min) was 4.90 l/h, and 0.0654 × CLcr if CLcr was < 80 ml/min. The apparent volume of the central compartment was 47.76 l and no covariate was found to affect it. The results of bootstrap analysis were in agreement with the original parameters of the final model, and VPC of the final model demonstrated good predictability. Initial dosage regimens were developed based on the simulations of the population pharmacokinetic model.
  
  
  CONCLUSIONS
  A one-compartment model fitted the retrospective data and CLcr had a significant effect on drug clearance. Initial dosage regimens for vancomycin were proposed to provide some help to individual therapy for Chinese adult patients with different renal functions.
authors: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
authors: Chenhui
authors: C
authors: Deng
authors: Taotao
authors: T
authors: Liu
authors: Tianyan
authors: T
authors: Zhou
authors: Hua
authors: H
authors: Lu
authors: Daohai
authors: D
authors: Cheng
authors: Xiaobing
authors: X
authors: Zhong
authors: Wei
authors: W
authors: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D002681:China / Q000453:epidemiology; D003198:Computer Simulation; D003404:Creatinine / Q000097:blood; D054796:Drug Dosage Calculations; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D009010:Monte Carlo Method; D012189:Retrospective Studies; D014640:Vancomycin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D014640:Vancomycin; D003404:Creatinine