Intestinal drug degradation reactions

The bacteria in the intestinal tract serve as another well-known source of luminal drug degradation [61], though this is only important for the colon region as the luminal concentration of bacteria is 104 to 109-fold higher in the colon compared with the small intestine. Thus, this aspect is only relevant for drugs that reach this region, for example, due to poor permeability, slow dissolution or delivery by modified-release formulations. Hydrolytic and other reductive reactions are predominantly mediated by bacterial enzymes, and a list of the most prominent types... 

Ueda, T., Yamaoki, T., Miyamoto, M., Kimura, Y., Sasatani, H., and Kim, S.I., Baeterial reduction of azo compounds as a model reaction for the degradation of azo-eontaining polyurethane by the action of intestinal flora. Bull Chem. Soc. Jpn., 69 1139-1142 (1996). Krishnaiah, Y.S., Satyanarayana, S., and Prasad, Y.V., Studies of guar gum eompression-coated 5-aminosalicylic acid tablets for colon-specific drug delivery. Drug-Dev. Ind. Pharm., 25 651-657 (1999). 

Chemical transformations in the liver are greatly facilitated by the action of enzymes within the smooth endoplasmic reticulum of hepatocytes (often called the microsomal fraction). Phase I reactions (oxidation, reduction, and hydrolysis reactions) convert molecules into more polar forms that usually differ in biological activity from the parent form. Oxidation reactions occur primarily under the direction of a family of enzymes called P450- Non-specific esterases in the liver, plasma, and other sites catalyze the hydrolysis of esters, whereas amides are hydrolyzed in the liver. Protein drugs are often degraded by proteases and peptidases, which are abundant in many tissues, including the intestinal tract and plasma. Phase II reactions are conjugation reactions. 

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