| Popis: |
BackgroundExtended interval dosing (EID) of tobramycin is recommended for treatment of pulmonary exacerbations in adults and older children with cystic fibrosis (CF), but data are limited in patients less than 5 years of age.MethodsWe performed a retrospective population pharmacokinetic (PK) analysis of hospitalized children with CF ® using data from the first 48 hours of tobramycin treatment. Monte Carlo simulations were implemented to determine the fraction of simulated patients that met published therapeutic targets with regimens of 10-15 mg/kg/day once daily dosing.ResultsFifty-eight patients received 111 tobramycin courses (range 1-9/patient). A 2-compartment model best described the data. Age, glomerular filtration rate, and vancomycin coadministration were significant covariates on tobramycin clearance. The typical values of clearance and central volume of distribution were 0.252 L/hr/kg^0.75 and 0.308 L/kg, respectively. No once daily regimens achieved all pre-specified targets simultaneously in >75% of simulated subjects. A dosage of 13 mg/kg/dose best met the predefined targets of Cmax >25 mg/L and AUC24 of 80-120 mg*h/L.ConclusionsBased on our population PK analysis and simulations, once daily dosing of tobramycin would not achieve all therapeutic goals in young patients with CF. However, extended-interval dosing regimens may attain therapeutic targets in the majority of young patients. |
