Pharmacokinetic changes of irinotecan by intestinal alkalinization in an advanced colorectal cancer patient.

The prevention of irinotecan (CPT-11)-induced diarrhea, a well-known adverse reaction to the drug, by treatment with intestinal alkalinization has been carried out in patients with colorectal cancer in Japan. Under acidic conditions, CPT-11 and its active metabolite, SN-38, exists preferably as the lactone form, whereas both exist as the carboxylate form under basic conditions. It has been suggested that the lactone forms of both CPT-11 and SN-38 are diffused passively across the intestinal mucosal membranes, whereas the carboxylate forms are actively transported. The intestinal uptake rate of both forms appears to be pH sensitive under physiological conditions, but it remains unclear whether intestinal alkalinization treatment affects the pharmacokinetics of CPT-11 and SN-38. This study was designed to evaluate the pharmacokinetics of CPT-11 and SN-38 in a colorectal cancer patient with or without alkalinization treatment. We found that intestinal alkalinization significantly decreased the plasma levels of CPT-11 and SN-38. In particular, the AUC of SN-38 was markedly decreased to 56 from 107 ng.h/mL. Intestinal alkalinization was effective in preventing CPT-11-induced diarrhea, but this treatment changed the pharmacokinetics of CPT-11 and SN-38 in the body.