Nonlinear pharmacokinetics of CPT-11 in rats.
The pharmacokinetics of a new water-soluble derivative of camptothecin. 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), and its major metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), was investigated after i.v. administration of 1 to 40 mg/kg of CPT-11 to rats. The plasma concentration of CPT-11 decreased biexponentially. The area under the concentration-time curve increased nonlinearly as the dose increased. SN-38 was found in the plasma, bile, urine, and feces. The SN-38 level was maintained at 0.06 to 0.08 micrograms/ml for 0.5 to 5.5 h depending on the dose, followed by exponential decay. Thirty-three to 58% of the CPT-11 was excreted without metabolism into the bile and urine for 24 h. SN-38 was mainly excreted into the bile. Analysis of the clearance has shown nonlinear pharmacokinetics which was due to metabolic processes such as the conversion of CPT-11 to SN-38.
Kaneda
N
N
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Yokokura
T
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D005965:Glucuronates / Q000378:metabolism; D000077146:Irinotecan; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000972:Antineoplastic Agents, Phytogenic; D005965:Glucuronates; D000077146:Irinotecan; D002166:Camptothecin