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Population pharmacokinetics of amikacin in a Korean clinical population

Authors
 S.B. Jang  ;  Y.J. Lee  ;  M.S. Park  ;  Y.G. Song  ;  J.-H. Kim  ;  H.K. Kim  ;  B.S. Ahn  ;  K. Park 
Citation
 International Journal of Clinical Pharmacology and Therapeutics, Vol.49(6) : 371-381, 2011 
Journal Title
 International Journal of Clinical Pharmacology and Therapeutics 
ISSN
 0946-1965 
Issue Date
2011
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. MATERIALS AND 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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/93870
DOI
10.5414/CP201520
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
Yonsei Authors
김정호(Kim, Jeong Ho) ; 박경수(Park, Kyung Soo) ; 송영구(Song, Young Goo)
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http://www.dustri.com/nc/journals-in-english/mag/int-journal-of-clinical-pharmacology-and-therapeutics/vol/volume-49/issue/june-23.html
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