Study of the Pharmacokinetics and a Side-Effect Analysis of Irinotecan and its Metabolite

Abstract

The purpose of this study was to evaluate the distribution of CPT-11 and its active metabolite, SN-38, in both pleural and pericardial fluid after intravenous administration.
Two patients with lung cancer were intravenously treated with 60mg/m² CPT-11 on days 1, 8, and 15. The CPT-11 was detected in the pleural fluid 1.5 hrs after the start of intravenous infusion, and its level reached a maximum 24 hrs later. Similarly, the active metabolite SN-38 was detected in the pleural fluid 1.5 hrs after the start of intravenous infusion. In addition, the SN-38 concentration in the pleural fluid was almost as high as that in the plasma 24 hrs later. These results suggest that intravenously administered CPT-11 may penetrate into the thoracic cavity and therefore be metabolized into SN-38 there. The maximum concentrations of CPT-11 and SN-38 in the pleural fluid to the corresponding plasma levels were 20. 4 % and 28. 5%, respectively. In addition, the AUCs of the lactone form of SN-38 were much lower than that of the carboxyl form in the pleural fluid.
CPT-11, SN-38 and SN-38 glucronide all showed similar pharmacokinetics in the pericardium to that in plasma.