[Pharmacokinetics of etoposide short-term infusions within the scope of the GPOH therapy protocol].
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 micrograms.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 micrograms.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.
Boos
J
J
Universitäts-Kinderklinik, Pädiatrische Hämatologie/Onkologie, Münster.
Real
E
E
Schulze-Westhoff
P
P
Pröbsting
B
B
Wolff
J
J
Jürgens
H
H
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007223:Infant; D007260:Infusion Pumps; D007938:Leukemia / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy
D005047:Etoposide