Drug metabolism aromatic

Nakajima T, Sato A. 1979. Enhanced activity of liver drug-metabolizing enzymes for aromatic and chlorinated hydrocarbons following food deprivation. Toxicol AppI Pharmacol 50 549-556. 

Oxidation Aromatic Hydroxylation. Since many drugs contain aromatic rings, this is a very common metabolic transformation. The process tends to be species specific, with human showing a strong tendency to hydroxylation in the para position. This reaction proceeds via an arene epoxide intermediate. The anticonvulsant drug phenytoin is metabolized by being para-hydroxylated in its aromatic rings. 

Environmental chemicals and pollutants are also capable of inducing P450 enzymes. As previously noted, exposure to benzo[a]pyrene and other polycyclic aromatic hydrocarbons, which are present in tobacco smoke, charcoal-broiled meat, and other organic pyrolysis products, is known to induce CYP1A enzymes and to alter the rates of drug metabolism. Other environmental chemicals known to induce specific P450s include the polychlorinated biphenyls (PCBs), which were once used widely in industry as insulating materials and plasticizers, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin, TCDD), a trace byproduct of the chemical synthesis of the defoliant 2,4,5-T (see Chapter 56). 

Adverse environmental conditions or stimuli, which create stress in an animal, may influence drug metabolism and disposition. Cold stress, for instance, increases aromatic hydroxylation, as does stress due to excessive noise. It should be noted that the microsomal monooxygenases show a diurnal rhythm in both rats and mice, with the greatest activity at the beginning of the dark phase. 

A number of drugs having aromatic rings are metabolized by hydroxylation in the liver,225-227 e.g., in the metabolism of mepivacaine (368), isomeric 3-hydroxy (370) and 4-hydroxy compounds have been isolated, out of which 370 has been shown to be formed through the involvement of arene oxide 369.228... 

Metabolism of tricyclic drugs by aromatic hydroxylation and A-oxidation is of minor importance. 

Sulphate conjugates are formed with hydroxy compounds (e.g. alcohols and phenols) or aromatic amines. For example, morphine-3-(9-ethereal sulphate is a minor metabolite of morphine and N-phenylsulphamic acid is a metabolite of aniline. Sulphate conjugates are strong acids and are readily excreted in the urine they are of relatively little importance in drug metabolism. 

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