Population pharmacokinetics of tobramycin in hospitalized patients receiving once-daily dosing regimen

The population pharmacokinetics of tobramycin was investigated in a group o f 327 adult hospitalized patients receiving once-daily administration of to bramycin at a dose of 7 mg kg(-1). The patients had an average age of 57 +/ - 18 y and an average weight of 65 +/- 14 kg; 153 of the patients were fema le. Data, comprised of 575 serum concentrations, were analyzed using a nonl inear mixed-effect model (NONMEM) with a first-order conditional estimation method and were best described with a one-compartment model. The patient c ovariates including body weight, gender, age and creatinine clearance (CLCR ) were added in a stepwise fashion to identify their potential influences o n tobramycin pharmacokinetics. Results showed that tobramycin clearance (CL ) was linearly correlated with CLCR (proportionality constant: 0.066 +/- 0. 002 x CLCR (ml min(-1))) and the volume of distribution (V-d) was linearly related to body weight (proportionality constant: 0.40 +/- 0.024 x body wei ght (1 kg(-1))). The mean population estimates for CL and V-d were 4.53 1 h (-1) and 27.3 1, respectively. The half-life of tobramycin was estimated to be 4.2 h. The inter-individual variability in CL and V-d were 37.0 and 28. 5%, respectively. The residual error was 1.2 mg 1(-1). Based on the results , optimal dosing intervals for renal impaired patients were calculated and were comparable with the intervals derived from the previous established no mogram. (C) 2000 Elsevier Science B.V. and International Society of Chemoth erapy. All rights reserved.