Urinary kidney injury biomarkers and tobramycin clearance among children and young adults with cystic fibrosis: a population pharmacokinetic analysis

Tobramycin is frequently used for treatment of bronchopneumonia in patients with cystic fibrosis (CF). Variability in tobramycin clearance (CL) is high in this population with few reliable approaches to guide dosing. We sought to evaluate the pharmacokinetics of once-daily intravenous tobramycin in...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2017-01, Vol.72 (1), p.254-260
Main Authors: Downes, Kevin J, Dong, Min, Fukuda, Tsuyoshi, Clancy, John P, Haffner, Christopher, Bennett, Michael R, Vinks, Alexander A, Goldstein, Stuart L
Format: Article
Language:English
Subjects:
Administration, Intravenous
Adolescent
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - pharmacokinetics
Biomarkers - analysis
Bronchopneumonia - complications
Bronchopneumonia - drug therapy
Child
Creatinine - blood
Cystic Fibrosis - complications
Drug Monitoring
Female
Hepatitis A Virus Cellular Receptor 1 - analysis
Hospitals, Pediatric
Humans
Lipocalin-2 - urine
Male
Metabolic Clearance Rate
Ohio
Original Research
Pilot Projects
Prospective Studies
Renal Insufficiency, Chronic - diagnosis
Renal Insufficiency, Chronic - pathology
Retinol-Binding Proteins - urine
Tobramycin - administration & dosage
Tobramycin - pharmacokinetics
Young Adult
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Summary:Tobramycin is frequently used for treatment of bronchopneumonia in patients with cystic fibrosis (CF). Variability in tobramycin clearance (CL) is high in this population with few reliable approaches to guide dosing. We sought to evaluate the pharmacokinetics of once-daily intravenous tobramycin in patients with CF and test the influence of covariates on tobramycin CL, including serum creatinine (SCr) and urinary biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), retinol-binding protein (RBP) and kidney injury molecule-1 (KIM-1). This was a prospective, observational cohort study of children/young adults with CF receiving once-daily intravenous tobramycin from October 2012 to May 2014 at Cincinnati Children's Hospital Medical Center. Therapeutic drug monitoring data were prospectively obtained. Population pharmacokinetic analyses were performed using non-linear mixed-effects modelling. Thirty-seven patients (median age 15.3 years, IQR 12.7-19.5) received 62 tobramycin courses. A one-compartment model with allometrically scaled weight for tobramycin CL and volume of distribution (V) best described the data. Urinary NGAL was associated with tobramycin CL (P 
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkw351