[Mechanisms of drug metabolism--implications for drug interaction]

Most drugs undergo biotransformation before excretion by renal, biliary or other routes. The main purpose of metabolism is to make the drug, which is usually lipophilic, more water soluble. Metabolic reactions, depending upon the end product formed, can be classified as functionalisation (phase I) or conjugation (Phase II) reactions. Phase I metabolic reactions include oxidation, reduction and hydrolysis; while phase II processes are glucuronidation, sulfation, methylation, acetylation and mercapture formation. Cytochrome P-450 isozymes play a central role in metabolism of great majority of xenobiotics, as well as some endogenous substances. Many drugs can inhibit, induce and alter relative amounts of different P-450 enzymes; therefore, possibilities of drug-drug interactions exist in that one drug can influence biodisposition of another with potential clinical implications. One drug can inhibit metabolism of another, leading to excessive accumulation and toxicity. Alternatively, one drug can stimulate or induce metabolism of another drug resulting in subtherapeutic plasma levels of the later.