Pharmacologic effect of the drug results from its metabolism to metabolites showing decreased lipophilic properties and increased solubility in water. Transformations leading to inactivation of the drug are usually conducted by microsomal enzymes combined with cytochrome P-450. Main types of the metabolic reactions involved in the metabolism of exogenous substances are: oxidative reactions, hydrolysis and coupling reactions (often called second phase reactions). Estimation of the appearance of metabolites containing reactive groups (amino- or hydroxyl) should take into consideration the factor influencing the coupling reactions with glucuronic acid, sulphides, but also N-acetylation and methylation, coupling with glutathione or amino acids (mainly glycine and glutamine). Liver plays basic role in the metabolism of the drugs, but this metabolic activity appears also in the alimentary canal, where under influence of hydrochloric acid in stomach and intestine enzymes some xenobiotics are degraded. A special role is also played by intestine microflora.
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