EFFECT OF ELEVATED VISCOSITY IN THE UPPER GASTROINTESTINAL-TRACT ON DRUG ABSORPTION IN DOGS

The objectives of these studies were, first, to determine the effect o f elevated luminal viscosity on the gastrointestinal absorption of fou r model drugs and, second, to identify the key processes influencing d rug absorption under elevated viscosity conditions. Studies were condu cted in vitro and in healthy female mongrel does under fasting conditi ons. In the canine model, both the rate and extent of paracetamol and hydrochlorothiazide absorption were significantly decreased by the coa dministration of 15 g guar gum dissolved in 500 ml normal saline. In t he case of cimetidine, the rate but not extent of absorption was decre ased. Owing to the high variability in the data, no statistically base d conclusion could be drawn about the effects of coadministered guar g um on the oral absorption of the poorly soluble mefenamic acid. Based on the in vitro data, it appears that substantial reductions in the di ssolution rate of paracetamol, hydrochlorothiazide and cimetidine acco unt for the effects observed in vivo. It is concluded that the effect of an elevation in the intraluminal viscosity on drug absorption is gr eatest for highly soluble drugs, and results from a combination of a d ecrease in dissolution rate and gastric emptying rate. (C) 1998 Elsevi er Science B.V.