POPULATION PHARMACOKINETICS OF AMIKACIN IN INTENSIVE-CARE UNIT PATIENTS STUDIED BY NPEM ALGORITHM

The population pharmacokinetics of amikacin was studied in 40 intensiv e care unit patients (212 plasma concentrations) by NPEM algorithm usi ng a one-compartment model. The population was best characterized by t he following pharmacokinetic parameters: renal clearance relative to c reatinine clearance (C-s = 0.96 +/- 0.33), and either the total volume of distribution (V-d = 23.9 +/- 7.01) or the volume of distribution r elative to body weight (V-s = 0.36 +/- 0.10 l.kg(-1). The volume of di stribution was increased with respect to the usual value of 0.25 l.kg( -1). The statistical distribution of these pharmacokinetic parameters was approximately gaussian, with no significant correlation between vo lume of distribution and clearance. The medians and standard deviation s of C-s and V-s were used as reference population values to estimate the pharmacokinetics of amikacin in a second group of 29 patients by t he bayesian method, with two blood samples per patient. For each patie nt, the fitted parameters were able to predict the plasma concentratio ns of amikacin during the next 72 h with no significant bias and good precision (2.9 mg.l(-1) for peaks and 0.5 mg.l(-1) for troughs). This study confirms the ability of the NPEM algorithm to provide reference population values for use in bayesian monitoring of aminoglycoside the rapy.