title: Population pharmacokinetics of amikacin in a Korean clinical population.
abstract: OBJECTIVE
  This study aimed at investigating the influence of demographic and clinical covariates on the population pharmacokinetics of amikacin in Korean patients from routinely collected therapeutic drug monitoring data.
  
  
  METHODS
  Pharmacokinetics was studied in 305 adult Korean patients who received amikacin 125 - 1,000 mg once-daily or every-other- day. Peak and trough plasma levels of steady state were measured. Patients were randomized into an index dataset (n = 197) and a validation dataset (n = 108). Covariates were selected in a step-wise approach using NONMEM 7 software. The predictive performance of the model was evaluated by the percent prediction error and the percent coverage of 95% population prediction interval.
  
  
  RESULTS
  The covariates significantly influencing amikacin pharmacokinetics were creatinine clearance (p < 0.0001) and ward setting (p = 0.0017) for clearance, and body weight (p < 0.0001) and presence of cholecystitis (p = 0.0135) for volume of distribution. The estimates of pharmacokinetic parameters for a typical individual were 2.82 l/h for clearance, and 18.04 l for volume of distribution. Inter-individual variability (CV%) was 31% for clearance. The mean (SD) of percent prediction errors was 2.1 (26.4)% for peak and -121.5 (460.3)% for trough concentrations. Percent coverage of 95% PPIs for peak and trough concentrations were above 80%.
  
  
  CONCLUSIONS
  The population pharmacokinetic model developed in this study may be used as a basis for finding optimal amikacin dosing in a Korean patient population without a significant bias. Further studies will be needed to validate these results.
authors: Department of Pharmacology and Pediatrics, Internal Medicine, Laboratory Medicine in Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
authors: S B
authors: SB
authors: Jang
authors: Y J
authors: YJ
authors: Lee
authors: M S
authors: MS
authors: Park
authors: Y G
authors: YG
authors: Song
authors: J-H
authors: JH
authors: Kim
authors: H K
authors: HK
authors: Kim
authors: B S
authors: BS
authors: Ahn
authors: K
authors: K
authors: Park