uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Population Pharmacokinetics of Tobramycin in Patients With and Without Cystic Fibrosis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2013 (English)In: Clinical Pharmacokinetics, ISSN 0312-5963, Vol. 52, no 4, 289-301 p.Article in journal (Refereed) Published
Abstract [en]

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. Methods To investigate this issue, a population pharmacokinetic meta-analysis of data from eight centres was undertaken. NONMEM (R) 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. Results 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. Conclusion 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.

Place, publisher, year, edition, pages
2013. Vol. 52, no 4, 289-301 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-201262DOI: 10.1007/s40262-013-0036-yISI: 000318524800006OAI: oai:DiVA.org:uu-201262DiVA: diva2:626701
Available from: 2013-06-10 Created: 2013-06-10 Last updated: 2013-06-10Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text
By organisation
Department of Pharmaceutical Biosciences
In the same journal
Clinical Pharmacokinetics
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 185 hits
ReferencesLink to record
Permanent link

Direct link