I

1500 Time (minutes)

Figure 6.11 The transit of light and heavy pellets in ileostomy patients measured by gamma scintigraphy (ROI=region of interest)

1500 Time (minutes)

Figure 6.11 The transit of light and heavy pellets in ileostomy patients measured by gamma scintigraphy (ROI=region of interest)

gradient for hydrocortisone but not for triamcinolone46. Digoxin47 and hydrochlorthiazide38 have also been shown to be absorbed predominantly from the duodenum and upper jejunum. Although there is excellent absorption from the duodenum, transit through this area is extremely rapid, in the order of seconds16 and hence the actual amount of drug absorbed from this region will be small.

Cell monolayers formed from the human colon cancer cell line Caco-2 have been widely used to study the absorption of drugs48. Caco-2 cells form confluent and polarized monolayers when maintained in culture and differentiate towards the mature small bowel enterocyte phenotype. Caco-2 cell monolayers mimic intestinal absorptive epithelium and represent a very useful tool for studying transepithelial drug transport. However, some enzymes and transport systems are expressed to a lesser extent in Caco-2 cells compared to normal enterocytes49. Caco-2 cells also express various cytochrome P450 isoforms and phase II enzymes such as UDP-glucuronosyltransferases, sulphotransferases and glutathione-S-transferases, and hence they have been used study presystemic drug metabolism50.

Specific carriers for the transport of riboflavin and iron are found principally in the duodenum and jejunum, whereas carriers for bile acid and vitamin B12 are found mainly in the ileum. The acid microclimate is less obvious in the ileum, favouring the absorption of weak bases while discouraging the absorption of weak acids. Finally, the ileum contains more commensal bacteria than the duodenum and jejunum. In elderly subjects, the bacterial population in the ileum may be high enough to metabolize certain drugs thereby reducing their efficacy.

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