JAC Advance Access first published online on April 19, 2007
This version published online on April 24, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm097
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Pharmacokinetic modelling of a once-daily dosing regimen for intravenous tobramycin in paediatric cystic fibrosis patients
1 Department of Pharmacy Services, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada 2 Department of Pharmacy, The Hospital for Sick Children, Toronto, Ontario, Canada 3 Clinical Research Support Unit, Program in Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada 4 Division of Infectious Diseases, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada 5 Division of Microbiology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada 6 Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
Received 8 December 2006; returned 10 January 2007; revised 25 February 2007; accepted 5 March 2007
* Corresponding author. Tel: +1-416-813-7642; Fax: +1-416-813-7886; E-mail: james.tjon{at}sickkids.ca
Objectives: This study was designed to determine an optimal dose range for the once-daily dosing (ODD) of tobramycin in the treatment of an acute pulmonary exacerbation in paediatric cystic fibrosis (CF) patients. In addition, we aimed to assess whether certain patient characteristics affect tobramycin pharmacokinetics and, therefore, dosing.
Methods: Patient characteristics and pharmacokinetic parameters of patients receiving tobramycin three times daily from 1 January 1992 to 31 October 2005 were analysed using univariate analysis and multiple linear regression to determine statistically significant relationships and to derive dosing models. The binary partitioning method was used to derive critical values to determine stratification within the chosen dosing model.
Results: Using multiple linear regression, age and sex were significantly associated with the volume of distribution divided by the body weight (V/kg). By the binary partitioning method, the critical value for age was 13.75 years.
Conclusions: Age and sex were used to derive an ODD regimen for tobramycin in paediatric CF. Using a target peak concentration range of 25–35 mg/L, the initial dose for female CF patients at least 14 years of age was calculated to be 7 mg/kg/day given intravenously as a single daily dose. All other CF patients would receive an initial dose of 9 mg/kg/day given intravenously as a single daily dose. These dosing guidelines will require prospective evaluation for safety and efficacy.
Key Words: aminoglycosides , antibiotic usage , Pseudomonas aeruginosa
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