Pharmacokinetic profile of once daily intravenous tobramycin in children with cystic fibrosis

J Paediatr Child Health. 2006 Oct;42(10):601-5. doi: 10.1111/j.1440-1754.2006.00944.x.


Aim: Once-daily tobramycin in patients with cystic fibrosis (CF) is a more convenient dosing regimen than thrice daily dosing. There are limited data on the pharmacokinetic (PK) profile for once-daily tobramycin in patients with CF. The aim of this study was to define the PK parameters for once-daily tobramycin in children with CF and develop an algorithm for therapeutic drug monitoring dosing.

Methods: CF patients admitted to hospital were commenced on once-daily intravenous tobramycin (12 mg/kg/day) and ticarcillin/clavulinic acid. Serum tobramycin levels were taken at 30 min, 2-4 h and 12 h post dose. Data points for the PK model included: age, sex, weight, tobramycin dose, time of tobramycin doses and levels, tobramycin levels. WinNonMix was used to obtain the PK parameters.

Results: Forty-four children with 86 admissions who were aged 9 months-20 years were included. A one-compartment intravenous infusion model with first order elimination kinetics produced the best model. Population parameters were: volume of distribution (V(d)) = 0.267 L/kg (95% confidence interval (CL) 0.260-0.272), clearance (CL) 0.103 L/kg/h (95% CI 0.098-0.107) and half-life (t(1/2)) 1.82 (95% CI 1.77-1.88) h. Once the population model was established post hoc analysis was used to calculate individual subject predictions. Plots of individual prediction curves agreed well with observed values.

Conclusion: This study has established an algorithm for routine monitoring of once-daily tobramycin in children with CF. Satisfactory serum levels of tobramycin were obtained with a dose of 12 mg/kg/day and a regimen algorithm that uses only one measurement to monitor the plasma concentration is suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Algorithms*
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Child
  • Cystic Fibrosis / drug therapy*
  • Drug Administration Schedule
  • Humans
  • Injections, Intravenous
  • Tobramycin / administration & dosage*
  • Tobramycin / pharmacokinetics*


  • Anti-Bacterial Agents
  • Tobramycin