Population pharmacokinetics of amikacin in Korean adult patients

Abstract

Background To determine demographic and clinical covariates that affect amikacin pharmacokinetic parameters in Korean clinical population Methods For 200 Korean adult patients (115 men and 85 women), blood samples were drawn at the trough and peak steady-state plasma concentrations after multiple infusions of the drug. Amikacin concentration was analyzed by Fluorescence Polarization Immunoassay. Using one-compartment model, the clearance and volume of distribution of amikacin and their relevance to various covariates (creatinine clearance, sex, ward (intensive care unit vs general), disease diagnosed) were estimated by a nonlinear mixed effect model using the NONMEM software, with a stepwise addition method for covariate selection. Results Creatinine clearance had the most significant influence on amikacin pharmacokinetics (p << 0.0001 for clearance, p <0.0001 for volume of distribution). In particular, amikacin clearance was significantly influenced by ward (1.37 (1.18–1.56) for intensive care unit, 2.24 (2.09–2.39) for general) and urinary tract infection (UTI) (1.44 (0.85–2.03) for UTI, 2.13 (1.97–2.29) for no UTI), with numbers denoting mean values (95% confidence interval) (L/hr). Conclusions Our results suggest that a pharmacokinetic model incorporating clinically important covariates would be necessary for a nonbiased amikacin dosage individualization in Korean clinical population. Further study would be needed to verify the appropriateness of the model proposed here. Clinical Pharmacology & Therapeutics (2005) 77, P86–P86; doi: 10.1016/j.clpt.2004.12.220