Enzyme induction/inhibition environmental factors

To assess selectivity in the inducing and inhibiting effects of environmental factors (for example, dmg treatment) on the activity of the different P-450 enzymes. In one of such smdies, nifedipine, sparteine, mephenytoin and antipyrine were administered simultaneously to 15 healthy subjects, including four poor metabohzers of sparteine and four poor metabolizers of mephenytoin [6], They received the cocktail on three different occasions without pretreatment, after pentobarbital pretreatment and together with cimetidine. Concentrations of nifedipine, its pyridine metabolite, and of sparteine and its dehydro metabolite were measured in the plasma nifedipine metabohtes, sparteine, dehydrosparteine, 4-hydroxymephenytoin, antipyrine and its three major metabohtes were all measured in urine. The kinetic parameters obtained clearly indicated that nifedipine metabolism is very sensitive to pentobarbital induction (Fig. 4), whereas antipyrine metabolism is sensitive only to a moderate degree and sparteine metabolism is unaffected. Cimetidine inhibited the metabohc clearance of all three compounds to a similar extent and also inhibited renal clearance of sparteine, most likely at the level of tubular secretion. Urinary excretion of 4-... 

The activity (induction or inhibition) of various CYP enzymes is influenced by a variety of factors that have been identified to date. For example, genetic polymorphisms are most significant in CYP families lA, 2A6, 2C9, 2C19, 2D6, and 2E1. Nutrition effects have been documented in families lAl, 1A2, IBl, 2A6,2B6, 2C8, 2C9, 2C19, 2D6, and 3A4 (10, 11) smoking influences families lAl, 1A2, and 2E1 (12) alcohol influences family 2E1 (13) drugs influence families lAl, 1A2, 2A6,2B6,2C, 2D6, 3A3, and 3A4,5 and environmental xe nobio tics such as polycyclic aromatic hydrocarbons. 

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