Pharmacokinetics of etoposide with intravenous drug administration in children and adolescents

Background : 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. Methods : Pharmacokinetic studies of etoposide, given at doses of 60–200 mg/m 2 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. Results : Pharmacokinetic parameters (mean~SD) of the 14 patients (24 courses) who received etoposide 100 mg/m 2 were as follows: peak serum concentration (C max ), 18.5~6.4 μg/mL; trough serum concentration, 0.2~0.1 μg/mL; biological half‐life (T 1/2 ), 3.6~0.7 h; volume of distribution (Vd), 6.3~3.4 L/m 2 ; area under the etoposide serum concentration‐time curve (AUC), 129~38 hr•μg/mL; systemic clearance, 21.1~10.8 mL/min per m 2 . The T 1/2 , Vd, and AUC were not associated with age. An increase in etoposide dose per body surface area (BSA) was associated with increase in its C max and area under the time‐concentration curve (AUC). Wide interpatient variability in these parameters was demonstrated. Conclusion : 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 C max . A clear correlation between C max 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.