In situ intestinal absorption of a poorly water-soluble drug from mixed micellar solutions of bile salt and lipolysis products in rats.

The role of a bile salt (sodium taurocholate) and lipolysis products (monoglyceride and fatty acid) in the intestinal absorption of a poorly water-soluble drug, diazepam, was investigated. Absorption rates and bioavailabilities were determined with the in situ rat gut technique of Doluisio et al. and analyzing the diazepam concentrations in the luminal solution, intestinal membrane, blood and lymph. The absorption rate constant of diazepam decreased with the increase in bile salt concentration. Thus, although the bile salt increased the solubility of diazepam, the net effect was a decrease in apparent diazepam absorption rate. On the other hand, the lipolysis products incorporated in the bile salt micelles increased the solubility of diazepam without affecting the absorption rate constant, and as a result the apparent absorption rate of diazepam increased. In addition, the solubilized diazepam was absorbed almost uniformly throughout the small intestine. The drug solubilized in mixed micelles of bile salt-lipolysis products was not absorbed through the lymphatic system along with the lipolysis products, rather it was absorbed directly into the blood. The possible mechanism of the effect of dietary fat in the absorption of drug is discussed.