Once-daily gentamicin dosing in children with febrile neutropenia resulting from antineoplastic therapy

Abstract

Study objectives: To evaluate an existing once-daily gentamicin dosing guideline in children with febrile neutropenia resulting from antineoplastic therapy and, if necessary, to develop a new simulated dosing guideline that would achieve pharmacokinetic targets more reliably after the first dose.

Design: Pharmacokinetic analysis of data from a retrospective medical record review.

Setting: Hematology-oncology unit of a university-affiliated pediatric hospital in Canada.

Patients: One hundred eleven patients aged 1-18 years who received once-daily gentamicin between April 2006 and January 2008 for the treatment of febrile neutropenia resulting from antineoplastic therapy, and who had plasma gentamicin concentrations determined after their first dose.

Measurements and main results: Demographic data, gentamicin dosing information, blood sampling times, and plasma gentamicin concentrations were noted. Plasma gentamicin concentrations were determined at approximately 3 and 6 hours after the start of the 30-minute infusion of the first dose. Pharmacokinetic parameters were calculated according to standard first-order, one-compartment equations. The proportion of children who achieved pharmacokinetic targets after the first gentamicin dose was used as a measure of dosing guideline performance; the guideline achieved maximum concentration (C(max)) values below the target range (20-25mg/L) in 51% of patients. Ideal dosing guidelines were then developed using the mean dose required to achieved a C(max) of 23 mg/L for each patient. Univariate analysis or the Student t test was used to determine the existence of significant relationships between pharmacokinetic parameters and patient age and sex. The recursive binary partitioning method was used to determine critical values of age for dosage guideline development; analysis of variance was then used to compare the different levels obtained after use of this technique. Simulated administration of once-daily gentamicin in the following doses achieved a C(max) within or above target in 73% of patients: 1 year to < 6 years, 10.5mg/kg/dose; girls > or = 6 years, 9.5mg/kg/dose; and boys > or = 6 years, 7.5mg/kg/dose. Doses were based on actual body weight for children who weighed less than 125% of ideal body weight or based on effective body weight for children 125% or more of ideal body weight.

Conclusion: The initial gentamicin dosing guidelines were not effective in achieving C(max). The new proposed dosing guidelines are predicted to achieve a C(max) within or above the target range in almost three quarters of patients. Subsequent dosing should be tailored according to plasma gentamicin concentrations.