Pharmacokinetics of etoposide with intravenous drug administration in children and adolescents

Abstract

Pharmacokinetics of etoposide in Japanese children and adolescents has not been investigated. The objectives of the present study were (i) to document the pharmacokinetics of etoposide in Japanese children; (ii) to determine the intra- and interpatient variability in systemic etoposide exposure and (iii) to obtain insights into the age-pharmacokinetic parameter relationship. Pharmacokinetic studies of etoposide, given at doses of 60-200 mg/m2 by intravenous (i.v.) route of administration, were conducted in 18 children and adolescents (aged <19 years) with malignant diseases. High performance liquid chromatography was used to measure the blood etoposide levels. Pharmacokinetic parameters (mean~SD) of the 14 patients (24 courses) who received etoposide 100 mg/m2 were as follows: peak serum concentration (Cmax), 18.5~6.4 microg/mL; trough serum concentration, 0.2~0.1 microg/mL; biological half-life (T1/2), 3.6~0.7 h; volume of distribution (Vd), 6.3~3.4 L/m2; area under the etoposide serum concentration-time curve (AUC), 129~38 hr x microg/mL; systemic clearance, 21.1~10.8 mL/min per m2. The T1/2, Vd, and AUC were not associated with age. An increase in etoposide dose per body surface area (BSA) was associated with increase in its Cmax and area under the time-concentration curve (AUC). Wide interpatient variability in these parameters was demonstrated. The present study demonstrated that: (i) Pharmacokinetics of etoposide in Japanese children and adolescents were similar to those in Caucasians. (ii) Increased exposure to etoposide was associated with the Cmax. A clear correlation between Cmax and AUC was also found. (iii) Selecting the dose of etoposide according to body surface area (BSA) might give an acceptable range of exposure for children more than 1 year of age.