Biotransformation processes Drug metabolism

With respect to drug-metabolizing enzymes, the majority of the CYPs responsible for phase I metabolism are concentrated in liver. The CYPs considered here are all found in the endoplasmic reticulum (isolated as microsomes ). Of the 18 human CYP families known, the bulk of xenobiotic biotransformation processes are carried out by enzymes from the CYP1, CYP2 and CYP3 families. In humans, realistically,... 

The enzymatic route which a drug or poison follows in its metabolism is very specific to the xenobiotic itself. Substances with the same type of structures need not go through the same pathway. And the "active" form of the drug or the "toxic" form of the poison may occur either at the beginning or during the course of transformation. Usually synthetic combinations are not active or toxic but many of their precursors are. The following diagram illustrates the possibilities of a biotransformation process. 

Enzyme induction The process wherein some drugs provoke cells to synthesize more drug-metabolizing enzymes, thus leading to accelerated drug biotransformation. 

A description of transdermal drug delivery has been produced which is based on the physicochemical properties of the permeant. At this time transdermal delivery is limited to the administration of potent drugs. Higher doses may be accessible if penetration enhancers are incorporated into the formulation. The kinetic model shows what properties these should have and that they are a function of the physico-chemical properties of the drug. Various loss processes, e.g. microbial biotransformation, skin enzyme metabolism can be identified but cannot, as yet, be quantified. 

Biotransformation or metabolic inactivation of drugs occurs mainly in the liver and, to a lesser extent, in the plasma, kidney, and other tissues, depending on the enzyme system involved. In the liver, microsomal enzymes catalyze many of the metabolic processes involved in the biotransformation of drugs. These metabolic processes may involve nonsynthetic reactions such as oxidation, reduction, or hydrolysis, or synthetic reactions, including conjugation, whereby the drug is coupled with an endogenous substrate (53). 

As described in Chapter Ih drug metabolism is composed of two distinct pathways of biochemical processing/ Phase I and Phase II. Phase I is a chemical modification (typically oxidatioiy hydrolysis/ or reduction reactions) performed primarily by members of the CYP enzyme family (49). Phase II metabolism consists of the biotransformation... 

Of the various pha.se I reactions that are considered in this chapter, oxidative biotransformation processes are, by far. the most common and important in drug metabolism. The general stoichiometry that describes the oxidation of many xenobiutics (R-H) to their corresponding oxidized metabolites (R-OH) is given by the following equation ... 

Nitrogen and oxygen functionalities are commonly found in most drugs and foreign compounds sulfur functionalities occur only occasionally. Metabolic oxidation of carbon-nitrogen. carbon-oxygen, and carbon-.sulfur systems principally involves two basic types of biotransformation processes ... 

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