LISTED INORDER OF APPROXIMATE AMOUNTS OF EACH ISOFORM IN HUMAN LIVER .
CYP 3A::
The 3A family is present in the largest quantities in human liver and it has been identified in extrahepatic tissues such as the gastrointestinal tract Three adult 3A isoforms have clear differences but overlap in their specificity considerably The system can be induced by phenobarbital rifampicin macrolide antibiotics and glucocorticoids Among the reactions catalyzed by 3A isoforms are erythromycin N-demethylation nifedipine oxidation 6b-hydroxylation and lidocaine N-demethylation The effect of grapefruit juice on metabolism of dihydropyridine calcium - channel blockers results from 3A inhibition by flavanoids in the drink
CYP 2D6 ::
The 2D6 isoenzyme debrisoquine hydroxylase is important clinically for several reasons It is responsible for metabolism of several drugs like Neuroleptics eg chlorpromazine fluphenazine perphenazine risperidone Antidepressants eg (imipramine desipramine nortriptyline clomipramine paroxetine ) Beta blockers Some antiarrhythmic agents Some oncolytic agents while not inducible by any known substance the system is subject to inhibition from quinidine and some neuroleptics producing noticeable interactions Differing phenotypes of 2D6 have been demonstrated and about 5%-10% of the Caucasian population are slow metabolizers Doses of drugs metabolized by this system should thus be decreased status is readily assessed through urine analysis following a 10-mg dose of debrisoquine The genetic locus producing decreased 2D6 activity cosegregates with the gene for sparteine oxidation As a result numerous drugs are affected by the two polymorphicaly expressed enzymes 4
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