Plasma pharmacokinetics of etoposide (VP-16) after i.v. administration to children

The pharmacokinetics of etoposide (VP-16), a semi-synthetic derivative of podophyllotoxin, were studied in 16 pediatric patients (median age 8.3 years; range 4 months to 22 years) including two girls with Down's syndrome (DS). The drug was administered as infusions (1-3 h) in a wide range of doses (9-322 mg, corresponding to 32-210 mg/m2). The area under the plasma concentration versus time curve (AUC), dose normalized by the body surface area, was independent of age, while AUC normalized by the dose in mg/kg increased with increasing age of the patients. The interpatient variability of AUC, normalized for the dose in mg/m2, was 23% (CV) compared to 32% (CV) normalized for the dose in mg/kg. The terminal half-life time was 4.1 h (median value; range 2.0-7.8 h). The pharmacokinetics of etoposide in children with DS and chromosomally normal children were very similar with regard to systemic drug exposure and plasma half-life time. From the pharmacokinetic point of view it was therefore not necessary to make any dose modifications in the two girls with DS. The two DS patients did not experience any enhanced degree of toxicity from their etoposide treatments. The results support that dosing of etoposide to children should be based on body surface area.