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Urinary kidney injury biomarkers and tobramycin clearance among children and young adults with cystic fibrosis: a population pharmacokinetic analysis.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2017 Jan; Vol. 72 (1), pp. 254-260. Date of Electronic Publication: 2016 Sep 01. - Publication Year :
- 2017
-
Abstract
- Background: 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.<br />Objectives: 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).<br />Methods: 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.<br />Results: 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 < 0.001), as was urinary RBP (P < 0.001). SCr, estimated glomerular filtration rate and urinary KIM-1 were not significant covariates. The population pharmacokinetic parameter estimates were CL = 8.60 L/h/70 kg (relative standard error 4.3%) and V = 31.3 L/70 kg (relative standard error 4.7%).<br />Conclusions: We describe urinary biomarkers as predictors of tobramycin CL using a population pharmacokinetic modelling approach. Our findings suggest that patient weight and urinary NGAL or RBP could be used to individualize tobramycin therapy in patients with CF.<br /> (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Administration, Intravenous
Adolescent
Anti-Bacterial Agents administration & dosage
Bronchopneumonia complications
Child
Creatinine blood
Drug Monitoring
Female
Hepatitis A Virus Cellular Receptor 1 analysis
Hospitals, Pediatric
Humans
Lipocalin-2 urine
Male
Ohio
Pilot Projects
Prospective Studies
Renal Insufficiency, Chronic diagnosis
Retinol-Binding Proteins urine
Tobramycin administration & dosage
Young Adult
Anti-Bacterial Agents pharmacokinetics
Biomarkers analysis
Bronchopneumonia drug therapy
Cystic Fibrosis complications
Metabolic Clearance Rate
Renal Insufficiency, Chronic pathology
Tobramycin pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 72
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 27585963
- Full Text :
- https://doi.org/10.1093/jac/dkw351