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

The pharmacokinetics of etoposide (VP-16), a semi-synthetic derivative of p odophyllotoxin, 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/m(2)). The area under the plasma conce ntration versus time curve (AUC), dose normalized by the body surface area, was independent of age, while AUC normalized by the dose in mg/kg increase d 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) normal ized for the dose in mg/kg. The terminal half-life time was 4.1 h (median v alue; range 2.0-7.8 h). The pharmacokinetics of etopside in children with D s and chromosomally normal children were very similar with regard to system ic drug exposure and plasma half-life time. From the pharmacokinetic point of view it was therefore not necessary to make any dose modifications in th e two girls with DS. The two DS patients did not experience any enhanced de gree of toxicity from their etoposide treatments. The results support that dosing of etoposide to children should be based on body surface area. [(C) 2000 Lippincott Williams & Wilkins.].