Effect of fractionated ifosfamide on the pharmacokinetics of irinotecan in pediatric patients with osteosarcoma.
The combination of irinotecan (daily for 5 days for 2 consecutive weeks) and ifosfamide (daily on days 1 through 3) was investigated in children with osteosarcoma. Irinotecan pharmacokinetic investigations were performed before ifosfamide (day 1), after 3 days of ifosfamide (day 3), and 9 days after the end of ifosfamide (day 12). On day 3, the concentrations of irinotecan's active metabolite, SN-38, were below the limit of quantitation in two patients and were decreased in a third patient. The SN-38 area under the concentration-time curve remained below the day 1 value in two patients on day 12. The reduced area under the curve to the active metabolite SN-38 during ifosfamide therapy predicts a compromised efficacy of irinotecan in this combination.
Crews
Kristine R
KR
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Stewart
Clinton F
CF
Liu
Tiebin
T
Rodriguez-Galindo
Carlos
C
Santana
Victor M
VM
Daw
Najat C
NC
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000077146:Irinotecan; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy*; D010599:Pharmacokinetics
D000077146:Irinotecan; D007069:Ifosfamide; D002166:Camptothecin