Document Detail

Population pharmacokinetics of tobramycin in patients with and without cystic fibrosis.
MedLine Citation:
PMID:  23420517     Owner:  NLM     Status:  MEDLINE    
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(®) 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.
Stefanie Hennig; Joseph F Standing; Christine E Staatz; Alison H Thomson
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Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Clinical pharmacokinetics     Volume:  52     ISSN:  0312-5963     ISO Abbreviation:  Clin Pharmacokinet     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-22     Completed Date:  2013-09-03     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  7606849     Medline TA:  Clin Pharmacokinet     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  289-301     Citation Subset:  IM    
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MeSH Terms
Age Factors
Aged, 80 and over
Anti-Bacterial Agents / administration & dosage*,  blood,  pharmacokinetics*,  therapeutic use
Child, Preschool
Cystic Fibrosis / drug therapy,  metabolism*
Dose-Response Relationship, Drug
Infant, Newborn
Middle Aged
Models, Biological*
Models, Statistical
Multicenter Studies as Topic
Predictive Value of Tests
Sex Factors
Tissue Distribution
Tobramycin / administration & dosage*,  blood,  pharmacokinetics*,  therapeutic use
Young Adult
Grant Support
G1002305//Medical Research Council; P41-EB01975/EB/NIBIB NIH HHS
Reg. No./Substance:
0/Anti-Bacterial Agents; VZ8RRZ51VK/Tobramycin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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