Phase I metabolism

The kinetic properties of chemical compounds include their absorption and distribution in the body, theit biotransformation to more soluble forms through metabolic processes in the liver and other metabolic organs, and the excretion of the metabolites in the urine, the bile, the exhaled air, and in the saliva. An important issue in toxicokinetics deals with the formation of reactive toxic intermediates during phase I metabolic reactions (see. Section 5.3.3). 

Phase I metabolism The introduction of a polar group, e.g. an hydroxyl group, into a parent drug strucmre prior to its elimination from the body. 

Beyond phase I metabolism, clozapine is a substrate for UTT1A4 and polymorphisms have already been identified in Japanese populations (Mori et al., 2005). Presumably other populations will display some variability. How this relates to everyday clinical practice is as yet unknown. 

Metabolism J. Hepatic blood flow J. Liver size J. Phase I metabolism 1 Incidence liver dysfunction T t /2 hepatically extracted drugs... 

Virtually all organisms possess biotransformation or detoxification enzymes that convert lipophilic xenobiotics to water-soluble and excretable metabolites (Yu et al. 1995). In the metabolic process, PAHs are altered by Phase I metabolism into various products such as epoxides, phenols,... 

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 phase-I metabolism of bambuterol is complex and involves both oxidation and hydrolysis. In human plasma, hydrolysis rapidly yields the monocarbamate metabolite, and then, slowly, terbutaline [164a], The reaction is catalyzed mainly by the nonspecific cholinesterase (EC 3.1.1.8) found in plasma [166]. In addition, cytochrome P450 catalyzed hydroxylation of an... 

Kassahun K, Davis M, Hu P, Martin B, Baillie T. (1997) Biotransformation of the naturally occurring isothiocyante sulforaphane in the rat Identification of phase I metabolities and glutathione conjugates. Chem Res Toxicol 10 1228-1233. 

Age-related changes in phase I metabolism coupled with the use of multiple medications place older patients at increased risk for adverse drug reactions. Adverse drug reactions occur due to either inhibition or induction of CYP enzymes, especially CYP3A, which is believed to be involved in the metabolism of more than one half of the currently prescribed drugs.Clinical outcomes are determined by... 

Phase I metabolic reactions involve oxidation, reduction, or hydrolysis of the parent molecule, resulting in the formation of a more polar compound. Phase 1 reactions are mediated by the cytochrome P450 (GYP) family of enzymes. While metabolism used to be thought of as the body s detoxification process, phase I metabolites may be equally or even more pharmacologically active than the parent compound. Drug metabolism in general, and CYP-based mechanisms in particular, are discussed in detail in Chapter 5. 

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