Abstract
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 µg/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.
Footnotes
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↵1 To whom requests for reprints should be addressed.
- Received July 20, 1989.
- Revision received November 28, 1989.
- ©1990 American Association for Cancer Research.
Volume 50, Issue 6
