C. Reppas et al., EFFECT OF ELEVATED VISCOSITY IN THE UPPER GASTROINTESTINAL-TRACT ON DRUG ABSORPTION IN DOGS, European journal of pharmaceutical sciences, 6(2), 1998, pp. 131-139
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.