Generally, the usual net effect of biotransformation may be said to be one of inactivation or detoxication, the duration and intensity of a xenobiotic’s actions being influenced (sometimes predominantly) by its rate and extent of metabolism. There are, however, numerous examples in which biotransformation does not result in inactivation; many drugs generate active metabolites and moreover, in a few instances activity derives entirely from the metabolite. The production of an active metabolite may therefore be beneficial, or it may be detrimental when it is the origin of undesirable (adverse) effects there are also examples in which the parent drug has little or no activity of its own but is instead converted to an active metabolite. A particular case of ‘inactive’ drugs that yield active metabolites is represented by the well-known prodrugs. When a delayed or prolonged response to a drug is desired (or an unpleasant taste or local reaction is to be avoided), it is a common pharmaceutical practice to prepare an inactive (or non-offending) precursor, such that the active form may be generated in the body. This practice has been termed drug latentiation. Examples of such precursors include chloramphenicol palmitate, dichlorphenazone and the estolates of various steroid hormones. Transformation of a drug, or other xenobiotic, into a toxic metabolite, on the other hand, is effected by a toxication reaction. Toxic responses from such a metabolite may manifest at a number of levels, ranging from the molecular to that of an organ or organism, with the former not necessarily implying the latter. What can be stated is that metabolic toxication processes are always counterbalanced by competitive and/or sequential detoxication processes that may lead to inactivation of the toxic metabolite.

A great number of physiological and pathological factors affecting drug metabolism have been characterized; these are of importance both in drug research and toxicology .Among the inter-individual factors we stress the species differences determined by genetic differences; the consequences of this genetic polymorphism are a greatly impaired metabolism of drugs (or prodrugs), and a marked risk of adverse reactions .Pharmacogenetics has thus become in recent years a major issue in clinical pharmacology and pharmacotherapy. Intra-individual factors are related to physiological changes or pathological states (affecting for example the hormonal balance and immunological mechanisms of individuals). Biological rhythms (still not always duly recognized) are of the utmost importance and their study is the realm of chronopharmacology. There are, however, factors from outside the body (intimately connected with the intra-individual factors) that can also have a profound influence on drug metabolism. Physical exposure to these factors can be either deliberate (e.g. alcohol, tobacco smoke, substances taken as food) or accidental (from air, water, different pollutants). Usually, the first group falls into the category of dietary factors while the second group comprises environmental factors. Factors of even greater significance (as far as drug therapy and toxicology are concerned) are enzyme induction and enzyme inhibition.

Best Regards,
Nancy Ella
Editor-In-Charge
Drug Designing: Open Access