Population pharmacokinetics of tobramycin in hospitalized patients receiving once-daily dosing regimen.
The population pharmacokinetics of tobramycin was investigated in a group of 327 adult hospitalized patients receiving once-daily administration of tobramycin 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 female. Data, comprised of 575 serum concentrations, were analyzed using a nonlinear mixed-effect model (NONMEM) with a first-order conditional estimation method and were best described with a one-compartment model. The patient covariates including body weight, gender, age and creatinine clearance (CL(CR)) were added in a stepwise fashion to identify their potential influences on tobramycin pharmacokinetics. Results showed that tobramycin clearance (CL) was linearly correlated with CL(CR) (proportionality constant: 0.066+/-0.002 x CL(CR) (ml min(-1))) and the volume of distribution (Vd) was linearly related to body weight (proportionality constant: 0.40+/-0.024 x body weight (1 kg(-1))). The mean population estimates for CL and Vd were 4.53 l h(-1) and 27.3 l, respectively. The half-life of tobramycin was estimated to be 4.2 h. The inter-individual variability in CL and Vd were 37.0 and 28.5%, respectively. The residual error was 1.2 mg l(-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 nomogram.
Xuan
D
D
Department of Pharmacy Research, Hartford Hospital, CT 06102, USA. dxuan@harthosp.org
Lu
J F
JF
Nicolau
D P
DP
Nightingale
C H
CH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007297:Inpatients; D016013:Likelihood Functions; D008875:Middle Aged; D008954:Models, Biological; D011153:Population; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D014031:Tobramycin