Cimetidine selective enzyme inhibition

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-... 

As discussed above, the analgesic effect of codeine depends greatly on its abihty to be metabolized to morphine. In patients in whom large amounts of codeine have been administered without relief, the possibility of a polymorphism of the CYP2D6 enzyme must be considered. Medications that inhibit CYP2D6 may reduce or even completely block the conversion of codeine to morphine. These include selective serotonin reuptake inhibitors (SSRls), cimetidine, and antidepressants such as buproprion. On the other hand agents that induce CYP450 isozymes, such as rifampin and dexamethasone, increase the conversion rate and increase the risk of adverse events. 

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