Effect of α- or β-Cyclodextrin on Gastrointestinal Absorption of Barbituric Acid Derivatives

Abstract

The effect of .alpha.- and .beta.-cyclodextrin on the intestinal absorption of barbituric acid derivatives (BA) [allobarbital, amobarbital, barbital, pentobarbital and phenobarbital] with the everted rat small intesting in vitro. The absorption apparently depended on the concentration of BA in mucosal solution. Cyclodextrins were useful for increasing the solubility of BA and hardly interfered with permeation of BA through the everted rat small intestine. The highest concentration of BA was available in .alpha.-cyclodextrin solution, but by comparison in the same amount, .beta.-cyclodextrin was more effective than .alpha.-cyclodextrin on increasing the solubility of BA. Complexes of .beta.-cyclodextrin and BA were prepared, and BA absorption from each complex solution was compared with that from the corresponding BA solution. The absorption of BA from complex solution exceeded that from Ba solution since the complex is more soluble than BA itself. Blood levels in rabbits after oral administration of BA and its .beta.-cyclodextrin complexes were compared. The solubility difference between BA and its complexes apparently has an effect on the bioavailability of BA.