PHARMACOKINETICS OF SHORT-TERM ETOPOSIDE INFUSIONS IN THE GPOH THERAPEUTIC PROTOCOLS

Important interpatient variability of etoposide pharmacokinetics during continuous infusion has been reported and drug level targeting, therefore, been suggested. The current German therapeutic protocols are mainly based on short-term infusion. We determined pharmacokinetic parameters during short-term infusion in 18 children aged between 10/12 and 17 years on different therapeutic schedules in order to investigate interpatient variability. The dosages ranged from 66 to 200 mg/m2. In the subgroup of patients who received 150 mg/m2 (n = 10) the AUC was 106 +/- 15 mug.h/ml (range 82-139), clearance 24 +/- 3 ml/min/m2 (18-31), t1/2 3.5 +/- 0.4. To compare kinetic data of all 21 courses in 18 children, standard AUC was calculated (AUC/100 mg/m2). The AUC then was (68 +/- 17 mug.h/ml)/(100 mg/m2). Half-life was 3.3 +/- 0.7 h and total clearance 26 +/- 6 ml/min/m2, respectively. In 5 courses in children < 2 years ( < 10 kg), pharmacokinetic parameters were within the normal range. In this group dosage was calculated per kg. Dose reduction of 31% (mean) resulted in 22% (mean) lower AUC's. In conclusion, interpatient variability of etoposide pharmacokinetics during short-term infusion is limited. Dose reduction in children < 2 years is not substantiated by our pharmacokinetic data.