Prevention of Irinotecan-Induced Diarrhea by Oral Sodium Bicarbonate and Influence on Pharmacokinetics

Authors:
  • KYKoichi Yasutake
    Koichi Yasutake
  • HNHogara Nishisaki
    Hogara Nishisaki
  • TNTakatoshi Nakashima
    Takatoshi Nakashima
  • KHKazutugu Horita
    Kazutugu Horita
  • SHSigeya Hirohata
    Sigeya Hirohata
  • AIArata Ishii
    Arata Ishii
  • KHKenichi Hamano
    Kenichi Hamano
  • NANobuo Aoyama
    Nobuo Aoyama
  • DSDaisuke Shirasaka
    Daisuke Shirasaka
  • TKTakashi Kamigaki
    Takashi Kamigaki
  • MKMasato Kasuga
    Masato Kasuga
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Abstract
Alkalization of the intestinal tract by oral administration of sodium bicarbonate has been reported to be a promising method for preventing delayed diarrhea, a dose-limiting toxicity in patients receiving chemotherapy with irinotecan hydrochloride. However, it is feared that this method may adversely affect the pharmacokinetics of irinotecan by inhibiting its intestinal absorption and that of its active metabolites. We compared the pharmacokinetics and toxicity of irinotecan with and without oral alkalization in a cross-over study that enrolled 10 colorectal cancer patients. We found that alkalization did not decrease the blood levels of irinotecan and its active metabolite. In fact, the area under concentration versus time curves (AUCs) of irinotecan and 7-ethyl-10-hydroxycamptothecin glucuronide (SN-38G) were statistically equivalent both with and without oral alkalization. Also, the AUC of SN-38 with alkalization was statistically equivalent or larger than that without alkalization. Oral alkalization reduced the incidence of diarrhea and gastrointestinal symptoms, and these adverse effects were not worsened by long-term administration. These results suggest that oral alkalization can control diarrhea and gastrointestinal toxicity without decreasing the blood levels of irinotecan and its active metabolites, thus improving the tolerability of long-term chemotherapy without reducing efficacy.

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