Site of drug absorption after oral administration: assessment of membrane permeability and luminal concentration of drugs in each segment of gastrointestinal tract.

This study was conducted to assess the site of drug absorption in the gastrointestinal (GI) tract after oral administration. Drug permeability to different regions of rat intestine, jejunum, ileum and colon, was measured by in situ single-pass perfusion method. It was revealed that the epithelial surface area should not be a determinant of the regional difference in the intestinal permeability of highly permeable drugs. Effects of the mucus layer at the surface of the epithelium and the fluidity of the epithelial cell membrane on the drug permeability were investigated. These factors are demonstrated to contribute to the regional differences in intestinal drug permeability. The luminal drug concentration in each segment of the GI tract after oral administration was measured directly in fasted rats. Water ingested orally was absorbed quickly in the jejunum and the luminal fluid volume was diminished in the middle to lower part of the small intestine. According to the absorption of water luminal concentration of atenolol, a drug with low permeability, was elevated and exceeded the initial dose concentration. In contrast, the concentration of highly permeable drugs, antipyrine and metoprolol, decreased quickly in the upper part of the intestine and a significant amount of drugs was not detected in the lower jejunum and the ileum. From the time-profiles of luminal drug concentration, fraction of dose absorbed from each segment of the GI tract was calculated. Both antipyrine and metoprolol were found to be absorbed quickly at the upper part of the small intestine. In addition, the possible contribution of gastric absorption was demonstrated for these drugs. The pattern of site-dependent absorption of atenolol showed the higher absorbability in the middle and lower portion of the jejunum. These informations on site-dependent absorption of drugs are considered to be important for effective oral delivery systems.