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.
Department of Pharmacy Research, Hartford Hospital, CT 06102, USA. dxuan@harthosp.org
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D
Xuan
J F
JF
Lu
D P
DP
Nicolau
C H
CH
Nightingale
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