title: Prevention of irinotecan-induced diarrhea by oral sodium bicarbonate and influence on pharmacokinetics.
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.
authors.affiliation: Department of Gastroenterology, Hyogo Medical Center for Adults, Hyogo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Yasutake
authors.forename: Hogara
authors.initials: H
authors.lastname: Nishisaki
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Nakashima
authors.forename: Kazutugu
authors.initials: K
authors.lastname: Horita
authors.forename: Sigeya
authors.initials: S
authors.lastname: Hirohata
authors.forename: Arata
authors.initials: A
authors.lastname: Ishii
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hamano
authors.forename: Nobuo
authors.initials: N
authors.lastname: Aoyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shirasaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamigaki
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy; D018592:Cross-Over Studies; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D017693:Sodium Bicarbonate / Q000008:administration & dosage* / Q000494:pharmacology*; D011795:Surveys and Questionnaires
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D017693:Sodium Bicarbonate; D002166:Camptothecin