Studies on the Metabolic Fate of CPT-11 (7):Pharmacokinetics in Rats following Consecutive Intravenous Doses.

Pharmacokinetic studies on blood level, tissue distribution and excretion of CPT-11, a new antitumor agent, were performed in rats during and after the consecutive intravenous administration of 14C-CPT-11 at a daily dose of 4mg/kg for 15 days.1. Blood levels of radioactivity at 24hr after daily dosing increased wit the number of doses. Blood concentrations at 24hr after the last closings of the 5th and 15th dose were 1.8 and 4.4 times higher than blood concentration at 24hr after the first dosing, respectively.2. Urinary and fecal excretion of radioactivity for 24hr after daily dosing (% of dose) was not significantly changed as the number of doses increased. In the group recieving 5 doses, 24.9 and 71.4% of radioactivity was excreted in urine and feces, respectively, during 72hr after the last dosing.3. As the number of doses increased, the concentration in m ost tissues, except pancras, increased slowly. After the last dosing, radioactivity tended to be slowly eliminated from the spleen, bone marrow, adrenal, mesenteric lymph node and ileum.