Oral versus intraperitoneal administration of irinotecan in the treatment of human neuroblastoma in nude mice.
The present study evaluated the plasma pharmacokinetics of irinotecan (CPT-11) and its effects against a human neuroblastoma in xenograft, given by different administration routes. One-third of the LD50 was administered either intraperitoneally (59 mg/kg mouse weight (MW)) or orally (404 mg/kg MW) to nude mice. The plasma levels of CPT-11 and its active metabolite SN-38 decreased rapidly when CPT-11 was administered intraperitoneally, but remained relatively high for 4-8 h after oral administration. Then, a human neuroblastoma xenograft was inoculated in another set of 21 nude mice. When the estimated tumor weight reached 150-200 mg, CPT-11 was administered in the total LD50 either intraperitoneally or orally in three doses at 4-day intervals (q4d x3) to the mice in each experimental group. Oral administration was found to be superior to intraperitoneal injection in terms of tumor inhibition and to be an effective route for CPT-11 administration in the treatment of human neuroblastoma in nude mice.
Choi
S H
SH
Department of Pediatric Surgery, University of Tokyo, Japan.
Tsuchida
Y
Y
Yang
H W
HW
D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D000077146:Irinotecan; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000097:blood / Q000188:drug therapy*
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin