The Effect of Micellar Solubilization on Mucosal Metabolism of Absorbed Glyceryl‐1‐monoether

Abstract

Summary. A lipid Jiiixture containing labelled oleic acid and labelled glyccrol-1-monoethcr was infused intraduodenally at a steady rate for 6 hours in unanaesthetized rats with l)iliary and thoracic dnct lymph fi.stulae. There were three groups, each of which received the same lipid mixture and dose but in dillerent physical states: miccllar in bile salts 10 mM, micellar in non-ionic detergent (Pluronic F68) and as a fine emulsion in bile salts 1 mM with no micellar phase. When a steady state of absorption had been reached the absorjition rate relati\e to area of small intestine utilized was greatest for micellar bile salt infusate and least for ni)n-niicellar enmlsion, with intermediate values for non-ionic micellar solution. There were differences in distdbiition of alxsorbed monoether label in the mucosa which suggested that metabolism of this model compound was affected by the rate of absorption. The percentage of monoether label which was saponifiable, i.e. which had been hydrolyzed and oxidized to fatty acid, was greater the more slowly the lipid was alxsorbed. On the other hand, the proportion of unsplit nionoethcr label which was estcrified wa.s smaller the more slowly the lipid was absorbed. .Since the results for non-ionic micellar infusate. containing no bilf salts, fell between those for high and low concentrations of bile salts, it seemed that metabolism of monoetber was uHected more by the absorptive Hnx rate than by a metabolic eftect of bile salts, per se.

Functions of Lipids for Enhancement of Oral Bioavailability of Poorly Water-Soluble Drugs

“…Although the specific mechanisms of absorption of the lipid digestion products have not been elucidated yet, the common role of the intestinal mixed micellar phase to solubilise these poorly water-soluble compounds and to provide a concentration gradient for absorption of lipids and presumably of drugs solubilised in this phase is generally accepted. Micelles are not absorbed intact, and lipids are suggested to be absorbed from a monomolecular intermicellar phase [9–11]. The dissociation of monomolecular lipids from the mixed micellar phase prior to absorption may be stimulated by a microclimate of lower pH at the intestinal absorptive site [12, 13].…”