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PubMed2003

Intestinal absorption of drugs mediated by drug transporters: mechanisms and regulation.

The absorption of drugs from the gastrointestinal tract is one of the important determinants for oral bioavailability. Development of in vitro experimental techniques such as isolated membrane vesicles and cell culture systems has allowed us to elucidate the transport mechanisms of various drugs across the plasma membrane. Recent introduction of molecular biological techniques resulted in the successful identification of drug transporters responsible for the intestinal absorption of a wide variety of drugs. Each transporter exhibits its own substrate specificity, though it usually shows broad substrate specificity. In this review, we first summarize the recent advances in the characterization of drug transporters in the small intestine, classified into peptide transporters, organic cation transporters and organic anion transporters. In particular, peptide transporter (PEPT1) is the best-characterized drug transporter in the small intestine, and therefore its utilization to improve the oral absorption of poorly absorbed drugs is briefly described. In addition, regulation of the activity and expression levels of drug transporters seems to be an important aspect, because alterations in the functional characteristics and/or expression levels of drug transporters in the small intestine could be responsible for the intra- and interindividual variability of oral bioavailability of drugs. As an example, regulation of the activity and expression of PEPT1 is summarized.

Journal Article↗
PubMed1987

Differential intestinal absorption of two fatty acid isomers: elaidic and oleic acids.

The absorption of 14C-labeled oleic acid and 14C-labeled elaidic acid was studied in bile- and pancreatic juice-diverted adult rats. In some cases these acids were compared with 14C-labeled palmitic acid absorption. Sodium taurocholate-emulsified test infusates containing an equimolar mixture of monopalmitin and two fatty acids (oleic and elaidic or palmitic), one of which was 14C labeled, were infused through a duodenal canula. The chyle was collected from the mesenteric lymphatic vessel by plastic tubing. Among the three fatty acids studied, oleic acid exhibited the highest lymphatic recovery rate (43-50%). Elaidic and palmitic acids appeared more slowly and in lesser amounts (10-17%). Simultaneously, the highest amount of chylomicrons was observed when the lipid emulsion contained oleic acid alone; the lowest was observed when elaidic acid was the only unsaturated fatty acid. Experimental data have also shown that compared with elaidic acid, oleic acid is preferentially incorporated into the lymph triglycerides. We can conclude from the data presented that the enterocytic enzymes involved in the absorption of lipids show a high degree of specificity related to the fatty acid isomery, since the absorption of elaidic acid differs markedly from its isomer oleic acid.

Animals↗
PubMed1987

Transient changes of the intestinal absorption of sodium and chloride in the rainbow trout after abrupt transfer into sea-water.

1. Unidirectional fluxes of Na+ and Cl-, ouabain-sensitive Na+,K+-ATPase activity and the protein content have been determined in the intestine of trout in fresh water (FW) and 1, 2, 7 days after sea-water (SW) transfer. 2. After abrupt transfer in SW the Na+ and Cl- transports follow in two phases: first, a permeabilization of the epithelium during the first day; secondly, a transient impermeabilization and increase of the protein content of the mucosa (2 days after SW transfer) and a progressive increase of both the unidirectional Na+, Cl- fluxes and the Na+,K+-ATPase activity (7 days after SW transfer). 3. After 7 days SW the adaptation of the enterocytes which is different for Na+ and Cl- and for the middle and the posterior intestine is not achieved.

Acclimatization↗