Stereoselective absorption and hydrolysis of cefuroxime axetil diastereomers using the Caco-2 cell monolayer model

Cefuroxime axetil, the orally active prodrug of cefuroxime is marketed as a 1:1 mixture of two diastereomers designated as R (1'R, 6R, 7R) and S (1'S, 6R, 7R). Prodrug hydrolysis is thought to occur during intestinal absorption, however little is known concerning the relative availability of cefuroxime from each isomeric form. The Caco-2 cell monolayer model was used to examine the possible stereoselectivity of absorption by measuring the accumulation and epithelial transport rate in the apical to basolateral direction of cefuroxime and cefuroxime axetil following application of the mixture (1.0 mM) or individual diastereomers (0.5 mM0 of cefuroxime axetil. Cefuroxime appearance in the basolateral chamber was in the order: mixture > R > S following application of the prodrug. The accumulation of unchanged cefuroxime axetil was S > R irrespective of the form applied, i.e. individual diastereomer or the mixture. Such stereoselective differences in both absorption and/or hydrolysis may contribute to the observed oral bioavailability (30-50%) of cefuroxime in vivo.