Improvement of absolute bioavailability of normally poorly absorbed drugs: inducement of the intestinal absorption of streptomycin and gentamycin by lipid-bile salt mixed micelles in rat and rabbit

Abstract

The effect of lipid—bile salt mixed micelles on the intestinal absorption of streptomycin and gentamycin was investigated in the loop of small and large intestine of rat. While bile salts micellar solutions did not enhance the absorption of aminoglycosides, their mixed micellar solutions including monoolein, oleic or lauric acid markedly enhanced their absorption. However, lecithin—bile salt mixed micellar solution did not affect the absorption. Pretreatment with mixed micellar solutions showed neither a direct action on the mucosal membrane nor a transient increase in permeability to aminoglycosides.Improvement of bioavailability in the rabbit was evaluated using various formulations and different routes of administration. In the rectal administration, not only mixed micellar solutions but also lyophilized mixed micelles powder improved bioavailability. The duodenal administration of mixed micellar solution, however, was not effective, indicating that enhanced absorption of drugs by mixed micelles may be more pronounced with rectal administration.