Effect of glutamine or alkaline ionized water on late diarrhea induced by irinotecan hydrochloride in Gunn rats

Purpose: Irinotecan hydrochloride (CPT-11) frequently develops early diarrhea, together with late diarrhea in patients. The present study was designed to determine whether glutamine (Gln) or alkaline ionized water (Alkali) could prevent and/or relieve late diarrhea induced by CPT-11 in Gunn rats, which lack the hepatic glucuronyltransferase activity. Method: Gunn rats (6 weeks old) were given Gln by oral administration at a dose of 0.4 g/(kg·d) or Alkali as free drinking water from 1 week before intravenous administration of CPT-11. The intravenous administration of CPT-11 was performed at a dose of 18 mg/kg via the femoral vein, followed by observation of the improved effect of these treatment on late diarrhea for 3 weeks. The body weight, food consumption, and fecal pH were also examined. Result: Treatment with Alkali or Gln prevented an increase of the diarrlea score, showed significant lower score compared with that of the control animals. Conclutions: The significant difference between the effects of Alkali and Gln could not be shown due to the marked inter-individual variations, even though Alkali seems to have more potential than Gln in antidiarrhea therapy. The diamine oxidase (DAO) activity during were measured for the 3 treatments (control, with treatmet by Alkali or Gln) during first course of the serial study. Pretreatment with Gln or Alkali reduced significantly serum DAO levels compared to that of control.

Keywords: Irinotecan hydrochloride Diarrhea Gunn rats Glutamine Alkaline ionized water