Pharmacokinetic modelling of a once-daily dosing regimen for intravenous tobramycin in paediatric cystic fibrosis patients.
OBJECTIVE
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.
Lam
Wallace
W
Department of Pharmacy Services, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
Tjon
James
J
Seto
Winnie
W
Dekker
Allison
A
Wong
Cecile
C
Atenafu
Eshetu
E
Bitnun
Ari
A
Waters
Valerie
V
Yau
Yvonne
Y
Solomon
Melinda
M
Ratjen
Felix
F
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D002648:Child; D003198:Computer Simulation; D003550:Cystic Fibrosis / Q000150:complications* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008171:Lung Diseases / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D015233:Models, Statistical; D009752:Nutritional Status; D010179:Pancreas / Q000503:physiopathology; D012189:Retrospective Studies; D018401:Sample Size; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D014031:Tobramycin