Tamura Takao, Yasutake Koichi, Nishisaki Hogara, Nakashima Takatoshi, Horita Kazutugu, Hirohata Sigeya, Ishii Arata, Hamano Kenichi, Aoyama Nobuo, Shirasaka Daisuke, Kamigaki Takashi, Kasuga Masato
Department of Gastroenterology, Hyogo Medical Center for Adults, Hyogo, Japan.
Oncology. 2004;67(5-6):327-37. doi: 10.1159/000082915.
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.
据报道，口服碳酸氢钠使肠道碱化是预防延迟性腹泻的一种有前景的方法，延迟性腹泻是接受盐酸伊立替康化疗患者的剂量限制性毒性。然而，人们担心这种方法可能会通过抑制伊立替康及其活性代谢物的肠道吸收而对其药代动力学产生不利影响。我们在一项纳入10名结直肠癌患者的交叉研究中比较了口服碱化和未口服碱化情况下伊立替康的药代动力学和毒性。我们发现碱化并未降低伊立替康及其活性代谢物的血药浓度。事实上，无论有无口服碱化，伊立替康和7-乙基-10-羟基喜树碱葡糖苷酸（SN-38G）的浓度-时间曲线下面积（AUC）在统计学上是等效的。此外，碱化情况下SN-38的AUC在统计学上与未碱化时等效或更大。口服碱化降低了腹泻和胃肠道症状的发生率，并且长期给药这些不良反应并未加重。这些结果表明，口服碱化可以控制腹泻和胃肠道毒性，而不降低伊立替康及其活性代谢物的血药浓度，从而在不降低疗效的情况下提高长期化疗的耐受性。
