Carrier-mediated transport systems compounds absorbed

On the other hand, several probe substrates of carrier-mediated transport systems in the small intestine have been reported to be not absorbed by carrier-mediated mechanism in the rat colon in situ. Those include L-carnitine [23], methotrexate [18], cephradine [18], and 5-fluorouracil [18], as substrates of the L-carnitine carrier, folate carrier, peptide carrier, and pyrimidine carrier, respectively (Table 3.3). It is based on the nonsaturable nature of their transport. Particularly, the apparent membrane permeabilities of L-carnitine and methotrexate are negligibly low, suggesting that these compounds are practically unabsorbable from the colon. In the case of 5-fluorouracil, Na+-independence of transport was observed in situ [18] and also in everted sacs in vitro in the colon [21], while its carrier in the small intestine is known to be Na+-dependent. Furthermore, for ascorbate and nicotinate, as described in everted sacs in vitro [21], and L-dopa, as described in situ [24], carrier-mediated transport cannot be observed in the rat colon. 

Distribution is the phase in which the compound is carried to tissues by the bloodstream or lymphatic system. Compounds are usually first absorbed into the portal venous system after oral administration directing them to the liver where they may be removed (extracted/metabolized) (first-pass effect). The blood (plasma) level reflects the concentration at the target/receptor and is governed by distribution. Distribution depends on passage through membranes (passive diffusion, carrier mediated transport etc.) and may be limited by binding to blood proteins. 

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