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  • Title: Adsorption of irinotecan onto oral adsorbent AST-120 (Kremezin) for preventing delayed diarrhea.
    Author: Hidaka M, Yamasaki K, Okumura M, Ogikubo T, Iwakiri T, Setoguchi N, Nishida K, Nagai K, Ikenoue T, Arimori K.
    Journal: Cancer Chemother Pharmacol; 2007 Feb; 59(3):321-8. PubMed ID: 16770581.
    Abstract:
    PURPOSE: One of the significant dose-limiting toxicities of irinotecan hydrochloride (CPT-11) is severe diarrhea due to impairment of the intestinal membrane induced by the excreted CPT-11 and its metabolites. AST-120 (Kremezin) is a prominent oral adsorbent that consists of porous spherical carbonic particles. To evaluate whether Kremezin can prevent the diarrhea induced by CPT-11, we investigated the adsorption characteristics of CPT-11 and its metabolites onto Kremezin in vitro and in vivo. METHODS: For in vitro studies, Kremezin was added to each solution containing one of the camptothecin drugs (CPT-11, SN-38, and SN-38-glucuronide), and adsorption activities were determined under various conditions. For in vivo studies, CPT-11 was consecutively administered, and the occurrence of diarrhea was compared between Kremezin-treated and non-treated rats. RESULTS: Kremezin drastically adsorbed the camptothecin drugs in vitro, and the adsorption percentages of the camptothecin drugs for 60 min were more than 85%. In addition, the frequency of diarrhea in Kremezin-treated rats decreased by approximately half of that in the non-treated rats. CONCLUSION: Kremezin showed potent adsorption capacities for the camptothecin drugs and mitigated the symptoms of diarrhea in rats. These results suggest that Kremezin is useful to prevent the diarrhea in clinical CPT-11 chemotherapy.
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