THE EFFECTS OF CHOLESTYRAMINE AND COLESTIPOL ON THE ABSORPTION OF DICLOFENAC IN MAN

The effect of oral administration of the non-absorbable anion-exchange resins cholestyramine and colestipol hydrochloride on the absorption of diclofenac in man was studied. Adsorption studies in vitro were als o performed. In a randomized crossover study consisting of three phase s, single doses of water suspensions of colestipol hydrochloride (10 g ), or cholestyramine (8 g), or water only were given to six healthy ma le volunteers immediately following ingestion of diclofenac (100 mg). After dosing, serial blood samples were collected for a period of 8 ho urs. Plasma harvested from blood was analyzed for diclofenac by a sens itive and accurate high-performance liquid chromatographic method. The area under the plasma concentration-time curve was moderately (33%, p < 0.05) reduced by colestipol, and greatly reduced (62%) by cholestyr amine. The maximum plasma concentration was reduced (58%) by colestipo l and even more (75%) by cholestyramine treatment. The in-vitro adsorp tion studies showed that colestipol has a weaker capacity for adsorpti on of diclofenac compared to cholestyramine. The in-vivo data suggest a reduction of diclofenac bioavailability when colestipol or cholestyr amine is administered concomitantly.