Biotransformation Metabolism, drug

In the 1970s, Smith and Rosazza introduced the concept of microbial models of mammalian metabolism [38,39]. Two reviews in this area were published in 1999 [40,41]. Since these, there have been numerous reports describing the use of microbial biotransformation in drug metabolism studies [42-54]. These reports demonstrated that microbial enzymes were able to... 

Metabolism The sum of anabolism and catabolism, although also used to describe the biotransformation of drugs in the liver. 

Fitzsimmons, M. E., Collins, J. M., Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4 potential contribution to high first-pass metabolism, Drug. Metab. Dispos. 1997, 25, 256-266. 

The terminator of drug action is, of course, elimination. Elimination is a composite of excretion (kidney, etc.) and biotransformation (metabolism). The primary measure of drug elimination from the whole body is clearance, CLt, defined as the volume of plasma fluid removed of drug per unit time. It is a direct measure of the loss of the drug from the system and can be calculated from Eq. (3.5) after IV administration of a dose of the drug. 

Interactions may occur at one or more of the various states in the pharmacokinetic pathways of drugs in the body (i.e., during absorption, distribution, biotransformation [metabolism], sites of action, and excretion). Each of these states is considered separately. 

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). 

Similar to many other cases of biologically active compounds, stereochemistry influences the pharmacological effect of a chiral drug. This can be explained by the fact that there is only one energeticaUy favorable (specific) interaction of an active molecule with its receptor, both being chiral structures. Qualitative and quantitative differences are caused by different receptor affinities as demonstrated in Fig, 1 (1). The metabolism (biotransformation) of drugs is mainly caused by enzymes, which are chiral macromolecules and discriminate between substrate molecules of different stereochemistry, This may result in metabolites of different activity and in different pharmacokinetics, resorption, and excretion. Therefore, racemic drugs should be looked on as a 1 1 mixture of two different compounds. 

Drug biotransformation (metabolism) Use of liver cells, homogenates or isolated cytochrome P450 isozymes to drug study biotransformation... 

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