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Pharmacokinetic studies on time -course of blood levels, tissue distribution and excretion of CPT-11, a new antitumor agent, were performed in male rats after a single intravenous administration of 14C-labeled CPT-11 at a dose of 4 mg/kg, 10.62mg/kg and 20mg/kg.1. The blood level of radioactivity at 5min after administration of the dose of 4mg/kg, 10.62mg/kg and 20mg/kg corresponded to 2.21μg/ml, 4.82μg/ml and 11.70μg/ml, respectively. The blood concentrations after these doses decreased multi-exponential ly in similar manner with the half-lives of 0.6-0.8 hr, 2hr and 16hr, respectively. The area under the concentration-time curve increased nonlinearly as the dose increased.2. The radioactivity was well distributed in all the tissues, especially in the kidney, adrenal, thyroid, pancreas and lung. The concentrations in these tissues were 13 to 25 times higher than that in the plasma. The radioactivity in most tissues, except skin, disappeared in a similar manner as that in the plasma.3. Within 72hr after the administration, the radioactivity was excreted into the urine and feces at the rate of 22. 2 and 76. 4% after the dose of 4mg/kg, 22.6 and 77.1% after administration of 10.62mg/kg, and 27.2 and 67.0% following administration of 20mg/kg, respectively.4. The pharmacokinetic profile of CPT-11 was also estimated by the whole body autoradiography.

Studies on the Metabolic Fate of CPT-11. (1): Pharmacokinetics in Rats following a Single Intravenous Dose. (1).