Population pharmacokinetics of tobramycin.

L. Aarons*, S. Vozeh, M. Wenk, P. Weiss, F. Follath

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

1. Population pharmacokinetic parameters of tobramycin were determined in a heterogenous group of 97 patients using serum samples drawn for the routine monitoring of tobramycin concentrations, following multiple dosing regimens. 2. To describe the accumulation kinetics of tobramycin a two‐compartment pharmacokinetic model was required. The best fit to the data was obtained when drug clearance (1 h‐1) was related linearly to creatinine clearance (proportionality constant: 0.059 +/‐ 0.002 x CLcr (ml min‐1)) and initial volume of distribution (1) was related linearly to body weight (proportionality constant: 0.327 +/‐ 0.014 x body weight (kg)). The intersubject variability in these two parameters was 32% and 3%, respectively, whilst the residual or intrasubject variability amounted to 21% of the tobramycin concentration. The terminal half‐life of tobramycin, 26.6 +/‐ 9.4 h, was appreciably shorter than previously reported. 3. The population pharmacokinetic model was validated against data obtained from 34 independent patients and the predicted and observed concentrations were found to be in good agreement. The population pharmacokinetic model was used to design a priori dosing recommendations for tobramycin. 1989 The British Pharmacological Society

Original languageEnglish
Pages (from-to)305-314
Number of pages10
JournalBritish Journal of Clinical Pharmacology
Volume28
Issue number3
DOIs
Publication statusPublished - Sept 1989
Externally publishedYes

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