Tobramycin in paediatric CF patients – TCI or

Aim: The aim of this study was to i) develop a population pharmacokinetic model for tobramycin in paediatric cystic fibrosis (CF) patients ii) evaluate the influence of covariates, in particular serum creatinine, and iii) test whether tobramycin in CF patients is a candidate for the use in target concentrations intervention (TCI).

Methods: Retrospective demographic, dosing and concentration data was collected from 35 cystic fibrosis patients (21 female) aged 0.5 – 17.8 years old from whom 318 tobramycin plasma concentrations were obtained during standard clinical care monitoring. Tobramycin concentrations were determined using an immunoassay (TDx). A nonlinear mixed-effect modelling approach (software: NONMEM) was used to describe the population pharmacokinetics of tobramycin.

Results: A two-compartment model best described the tobramycin data, with population parameter estimates for clearance of central compartment (CL) of 6.37 L/h/70 kg; volume of central compartment (Vc) of 18.7 L/70 kg; intercompartmental clearance (Q) of 0.393 L/h and volume of peripheral compartment (Vper) of 1.32 L. The inclusion of total body weight as covariate reduced the random component of between subject variability (BSV) in CL from 50.1% to 11.7% and in Vfrom 62.2% to 11.6%. The between occasion variability on CL was estimated in the final model as 6.5%.

Conclusions: This study provides the first pharmacokinetic model of once-daily IV tobramycin for the use of TCI in paediatric CF patients.