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Pharmacotherapy. 2004 May;24(5):564-73.

Tobramycin pharmacokinetics in children with febrile neutropenia undergoing stem cell transplantation: once-daily versus thrice-daily administration.

Author information

1
Department of Pharmacy, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada. lee.dupuis@sickkids.ca

Abstract

STUDY OBJECTIVE:

To describe the pharmacokinetic disposition of tobramycin in children undergoing stem cell transplantation (SCT) after intravenous administration either every 24 hours or every 8 hours, and to use this information to create initial dosing guidelines for administration every 24 hours in this patient population.

DESIGN:

Pharmacokinetic analysis of a randomized controlled trial.

SETTING:

The Hospital for Sick Children, Toronto, Ontario, Canada.

PATIENTS:

Sixty children (< 18 yrs) with febrile neutropenia undergoing stem cell transplantation.

INTERVENTION:

Patients were randomized to receive intravenous tobramycin either every 24 hours (29 patients) or every 8 hours (31 patients). Initially, they received either 2.5 mg/kg/dose every 8 hours or weight-based doses by age group (< 5 yrs, 9 mg/kg/dose; 5 to < 12 yrs, 8 mg/kg/dose; > or = 12 yrs, 7 mg/kg/dose) every 24 hours.

MEASUREMENTS AND MAIN RESULTS:

Serum tobramycin concentrations were obtained at 2 and 8 hours after the first dose. Initial guidelines for dosing every 24 hours were derived using the parameters from all patients to achieve a maximum serum concentration (Cmax) of 20-22.5 mg/L and a drug-free interval (time during dosing interval when the tobramycin concentration was < 1 mg/L) of at least 4 hours. After the first tobramycin dose, the elimination rate constant (kel) and volume of distribution (Vd) observed in the every-8-hour group (23 patients) were 0.34 +/- 0.09 hours(-1) and 0.48 +/- 0.21 L/kg, respectively. The kel and Vd in the every-24-hour group (22 patients) were 0.43 +/- 0.12 hr(-1) and 0.43 +/- 0.26 L/kg, respectively. Tobramycin Vd varied with age. Initial doses of tobramycin every 24 hours recommended to achieve the target parameters are 10 mg/kg/dose for patients aged 6 months to less than 9 years, 8 mg/kg/dose for those aged 9 to less than 12 years, and 6 mg/kg/dose for those aged 12 years or older.

CONCLUSION:

Children undergoing SCT who receive tobramycin every 24 hours should receive an initial dose based on age. Further validation of the proposed dosing guidelines is required.

PMID:
15162890
DOI:
10.1592/phco.24.6.564.34743
[Indexed for MEDLINE]

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