ISSN: 2041-6792

Clinical Investigation

Drug Metabolism Research Articles

 In the process of metabolism, drugs undergo "functionalization" and "conjugation" reactions, or both (Testa and Jenner, 1978). The former refers to the introduction, exposure or modification of specific chemical groups and is mediated by oxidation, reduction or hydrolysis. Conjugation involves linkage of the drug itself, or of a primary metabolite produced by a functionalization reaction, with endogenous compounds such as acetate, glycine, sulphate or glucuronic acid. The products usually, but not always, exhibit significantly enhanced watersolubility. Thomas and Meffin, 1972; Memn, Long and Thomas, 1973; Meffin and Thomas, 1973). Less easy, however, is an estimate of the relative contribution of each pathway to overall transformation. Furthermore, in the case of mepivacaine, one also has to contemplate the possibility that aromatic hydroxylation could be selective for one or other of the 3'- or 4'-positions; that is, regioselective metabolism may occur (Testa and Jenner, 1976b). As it happens, in man, both hydroxy compounds are excreted in the urine but at markedly different rates (Meffin and Thomas, 1973). Notice also that mepivacaine has an asymmetric carbon atom. Therefore, although the racemate is used clinically, metabolism of the component optical isomers may not be the same; the possibility of stereoselective metabolism of drugs becomes a further consideration (Jenner and Testa, 1973). Enzymes responsible for oxidation, reduction, hydrolysis and glucuronide formation are embedded in the endoplasmic reticulum of cell membranes and, on ultracentrifugation of sub-cellular components, they can be located in the so-called microsomal fraction.

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