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

摘要: BACKGROUND Tobramycin is frequently used for treatment of bronchopneumonia in patients with cystic fibrosis (CF). Variability tobramycin clearance (CL) high this population few reliable approaches to guide dosing. OBJECTIVES We sought evaluate the pharmacokinetics once-daily intravenous CF and test influence covariates on CL, including serum creatinine (SCr) urinary biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), retinol-binding protein (RBP) kidney injury molecule-1 (KIM-1). METHODS This was a prospective, observational cohort study children/young adults receiving from October 2012 May 2014 at Cincinnati Children's Hospital Medical Center. Therapeutic drug monitoring data were prospectively obtained. Population pharmacokinetic analyses performed using non-linear mixed-effects modelling. RESULTS Thirty-seven (median age 15.3 years, IQR 12.7-19.5) received 62 courses. A one-compartment model allometrically scaled weight CL volume distribution (V) best described data. Urinary NGAL associated (P < 0.001), as RBP (P < 0.001). SCr, estimated glomerular filtration rate KIM-1 not significant covariates. The parameter estimates CL = 8.60 L/h/70 kg (relative standard error 4.3%) V = 31.3 L/70 4.7%). CONCLUSIONS describe biomarkers predictors modelling approach. Our findings suggest that patient or could be individualize therapy CF.