Comparison of the pharmacokinetics and efficacy of irinotecan after administration by the intravenous versus intraperitoneal route in mice.
Irinotecan (CPT-11) is a new drug active in colorectal cancer. A comparison was made of the efficacy and pharmacokinetics of CPT-11 after i.p. versus i.v. administration to mice. We found that i.p. administration of CPT-11 to mice bearing C26 colon cancer was more efficient and less toxic than i.v. administration; a 100-mg i.p. dose induced an increase in life span equivalent to that produced by a 300-mg i.v. dose, and toxic deaths appeared after doses of 400 mg/kg given i.v. and 800 mg/kg given i.p. Pharmacokinetic parameters of CPT-11 and SN-38 were compared after i.v. or i.p. administration in mice bearing P388 leukemia ascites. Peritoneal CPT-11 and SN-38 AUC values were higher after i.p. administration than after i.v. injection. Plasmatic AUC values remained equivalent. Moreover, peritoneal CPT-11 clearance was 10-fold lower after i.p. versus i.v. administration. If the survival and pharmacologic advantage of i.p. CPT-11 in the murine model considered can be translated to a safe and practical mode of therapy in patients and if local toxicity does not prove to be a major adverse effect, then a potentially useful agent could be added to the drugs known to be active when given by the i.p. route for adjuvant therapy in colon cancer.
Guichard
S
S
Laboratoire de Pharmacologie, Institut Claudius Regaud, Toulouse, France.
Chatelut
E
E
Lochon
I
I
Bugat
R
R
Mahjoubi
M
M
Canal
P
P
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D000077146:Irinotecan; D051379:Mice; D008807:Mice, Inbred BALB C
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin