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  • Title: Nonlinear pharmacokinetics of CPT-11 in rats.
    Author: Kaneda N, Yokokura T.
    Journal: Cancer Res; 1990 Mar 15; 50(6):1721-5. PubMed ID: 2306726.
    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 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.
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