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Adsorption of irinotecan onto oral adsorbent AST-120 (KremezinTM) for preventing delayed diarrhea

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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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Acknowledgement

This study was supported in part by a Program for Strategic Regional Science and Technology Advancement.

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Authors and Affiliations

  1. Department of Pharmacy, Miyazaki Medical College Hospital, 5200 Kihara, Kiyotake-cho, Miyazaki-gun, Miyazaki, 889-1692, Japan

    Muneaki Hidaka, Keishi Yamasaki, Manabu Okumura, Tetsuya Ogikubo, Tomomi Iwakiri, Nao Setoguchi, Kentaro Nishida & Kazuhiko Arimori

  2. Department of Obstetrics and Gynecology, Miyazaki Medical College Hospital, Miyazaki, Japan

    Kimihiro Nagai & Tsuyomu Ikenoue

Authors
  1. Muneaki Hidaka
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  2. Keishi Yamasaki
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  3. Manabu Okumura
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  4. Tetsuya Ogikubo
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  5. Tomomi Iwakiri
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  6. Nao Setoguchi
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  8. Kimihiro Nagai
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  9. Tsuyomu Ikenoue
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  10. Kazuhiko Arimori
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Correspondence to Kazuhiko Arimori.

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Hidaka, M., Yamasaki, K., Okumura, M. et al. Adsorption of irinotecan onto oral adsorbent AST-120 (KremezinTM) for preventing delayed diarrhea. Cancer Chemother Pharmacol 59, 321–328 (2007). https://doi.org/10.1007/s00280-006-0273-y

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  • DOI: https://doi.org/10.1007/s00280-006-0273-y

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