Small intestine, drug absorption

LX Yu, GL Amidon. Saturable small intestinal drug absorption in humans Modeling and explanation of the cefatrizine data. Eur J Pharm Biopharm 45 199-203, 1998. 

These models are dependent on the temporal variable associated with the drug transit along the small intestine. Drug absorption phenomena are assumed to take place in the time domain of the physiological mean transit time. For those dynamic models that rely on diffusion-dispersion principles both the spatial and temporal variables are important in order to simulate the spat.iotemporal profile of the drug in the intestinal lumen. 

Tetracyclines, as broad-spectrum antibiotics, are the drugs of choice in treating Mycoplasma pneumoniae infections. Most tetracyclines are absorbed to various degrees (30 to 100%) from the gastrointestinal tract, primarily from the stomach and upper small intestine. The absorption of tetracyclines is hindered by milk and milk products, by numerous antacids such as aluminum hydroxide, sodium bicarbonate, and calcium carbonate, and by iron preparations such as ferrous sulfate. Therefore, these and similar substances should not be administered orally together with tetracycline (Figure 3.4). 

Pang, K. S., Komura, H., and Iwaki, M., Modeling of intestinal drug absorption roles of transporters and metabolic enzymes (for the Gillette Review Series), Species differences in in vitro and in vivo small intestinal metabolism of CYP3A substrates, Drug Metab. Dispos., 31(12), 1507, 2003. 

Since most drugs are largely absorbed in the upper part of the small intestine, drugs that alter the rate at which the stomach empties can affect absorption. Propantheline, for example, delays gastric emptying and reduces paracetamol (acetaminophen) absorption, (p.l92), whereas metoclopra-mide , (p.l91), has the opposite effect. However, the total amount of drug absorbed remains unaltered. Propantheline also increases the absorption of hydrochlorothiazide , (p.959). Drugs with antimuscarinic effects decrease the motility of the gut, thus the tricyclic antidepressants can increase the absorption of dicoumarol , (p.457), probably because they... 

If a drug is to be absorbed through the mucosal membranes that line the gut, then it must be in its lipophilic, un-ionised form in order to partition out of the aqueous medium. Gonsequently, acidic drugs tend to be absorbed more rapidly from the stomach, whilst basic drugs must pass through to the small intestine before absorption and the associated onset of action. The partition coefficient of the un-ionised form will also determine how much is absorbed. The absorption phase of the dose-response curve is therefore heavily influenced by the pKa and log P of a drug. 

Table 5 Influence of pH on Drug Absorption from the Small Intestine of the Rata... 

As mentioned previously, pH will also influence the absorption of an ionizable drug once it is in solution, as outlined in the pH partition hypothesis. Most drugs, however, are best absorbed from the small intestine regardless of pKa and pH. In some instances, especially lower down the GIT, there is the possibility of in-... 

LS Schanker, DJ Tocco, BB Brodie, CAM Hogben. Absorption of drugs from the rat small intestine. J Pharmacol Exp Ther 123 81-87, 1958. 

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