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

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.

journal_name

Pharmacotherapy

journal_title

Pharmacotherapy

authors

Dupuis LL,Sung L,Taylor T,Abdolell M,Allen U,Doyle J,Taddio A

doi

10.1592/phco.24.6.564.34743

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

564-73

issue

eissn

0277-0008

issn

1875-9114

journal_volume

pub_type

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