ABSTRACT
The influence of larger dose of pretreatment for seven days on the anti diabetic effect of glibenclamide and glipizide was studied. This study was conducted on alloxan induced diabetic rats of either sex, randomly distributed into 4 different groups. The first two groups were treated with acacia suspension 2%w/v and rabeprazole 40 mg/kg, p.o in 2% w/v gum acacia suspension for seven days and the other two groups (3 and 4) were treated with glibenclamide and glipizide respectively. The animals of the same groups were pretreated with rabeprazole (40 mg/kg) for 7 days. On eighth day, glibenclamide (200 μg/kg, p.o) and glipizide (200 μg/kg, p.o) were administered to respective groups one hour after treatment. Blood samples were collected from retro-orbital sinus at time intervals of 00, 1, 2, 4, 8, 12, 18, and 24 hrs and plasma glucose levels were estimated by GOD/POD method. The onset of glucose reduction, peak effect and duration of action were assessed. The study indicated that higher dose (around 8 times of therapeutic dose) of rabeprazole pretreatment has enhanced the anti diabetic effect of glibenclamide and glipizide significantly. Hence it is suggested that there is no possibility of occurrence of drug interaction during the concomitant usage of therapeutic doses of rabeprazole and sulfonylureas. Therefore the therapeutic drug monitoring and readjustment of the dose and frequency of administration of sulfonylureas are not essential at therapeutic dose levels.

Key words: Rabeprazole, glibenclamide, glipizide, alloxan, antidiabetic activity.