Population pharmacokinetics of tobramycin in patients with and without cystic fibrosis

Hennig, Stefanie, Standing, Joseph F., Staatz, Christine E. and Thomson, Alison H. (2013) Population pharmacokinetics of tobramycin in patients with and without cystic fibrosis. Clinical Pharmacokinetics, 52 4: 289-301. doi:10.1007/s40262-013-0036-y

Related Publications and Datasets
Author Hennig, Stefanie
Standing, Joseph F.
Staatz, Christine E.
Thomson, Alison H.
Title Population pharmacokinetics of tobramycin in patients with and without cystic fibrosis
Journal name Clinical Pharmacokinetics   Check publisher's open access policy
ISSN 0312-5963
Publication date 2013-02
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s40262-013-0036-y
Open Access Status
Volume 52
Issue 4
Start page 289
End page 301
Total pages 13
Place of publication Auckland, New Zealand
Publisher Adis International
Collection year 2014
Language eng
Formatted abstract
Background and Objectives
While several studies have examined the pharmacokinetics of tobramycin in patients with cystic fibrosis (CF), there is no consensus on whether they differ in patients with and without CF. The objectives of this study were to identify covariates which explain pharmacokinetic variability and to examine whether having the disease CF in itself alters these relationships and drug dose requirements.


To investigate this issue, a population pharmacokinetic meta-analysis of data from eight centres was undertaken. NONMEM® 7.2 was used to analyse the data, which comprised 4,514 concentration–time measurements from 465 adults and children with CF and 1,095 concentration–time measurements from 267 adults and children without CF.


Tobramycin disposition was well described by a two-compartment model with first-order elimination. Patient age, fat-free mass, serum creatinine concentration and sex were identified as significant covariates in the final model. Fat-free mass was superior to total bodyweight as a descriptor of clearance, volume of distribution of the central and peripheral compartments and inter-compartmental clearance. CF as an independent disease-specific factor had no significant influence on the pharmacokinetics of tobramycin at any stage during covariate model building. An optimal dose of 11 mg/kg every 24 h was defined for CF patients using a utility function approach.


The pharmacokinetics of tobramycin do not differ significantly in CF patients compared with patients without CF when subject age, fat-free mass, sex and renal function are taken into consideration. Variations in tobramycin dosing between CF and non-CF patients should therefore reflect target concentrations or exposures based on differences in expected pathogen sensitivity and not the presence of CF.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article in press; Published online 19 February 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Pharmacy Publications
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Created: Thu, 04 Oct 2012, 14:44:38 EST by Dr Stefanie Hennig on behalf of School of Pharmacy