Pharmacokinetics of irinotecan and its metabolites in human blood, bile, and urine.
Two patients were treated with CPT-11 for colorectal cancer and had a percutaneous biliary catheter for extrahepatic biliary obstruction. The first patient was treated with CPT-11 according to the 100-mg/m2 weekly therapeutic schedule, and the second patient was treated every 3 weeks, with a dose of 350 mg/m2 being given at the first course, after which it was decreased to 300 mg/m2 for the following courses. In plasma, the active identified metabolite of CPT-11, SN-38, occurred mainly in the form of a glucuronide conjugate. CPT-11 was mainly excreted in bile and urine as CPT-11. The cumulative biliary and urinary excretion of CPT-11 and its metabolites (SN-38 and SN-38 glucuronide conjugate) over a period of up to 48 h ranged from 25% (100 mg/m2 weekly) to 50% (300 mg/m2 every 3 weeks). This means that CPT-11 can be excreted under other, not yet identified metabolite forms.
Lokiec
F
F
Department of Pharmacology, Centre René Huguenin, Saint-Cloud, France.
Canal
P
P
Gay
C
C
Chatelut
E
E
Armand
J P
JP
Roché
H
H
Bugat
R
R
Gonçalvès
E
E
Mathieu-Boué
A
A
D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000493:pharmacokinetics*; D001646:Bile / Q000737:chemistry; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin