Metabohzer poor metabolizer

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 more adults with ADHD are being treated with methylphenidate, the possibility of drug interactions with methylphenidate increases (9). However, based on a study in extensive and poor CYP2D6 metabohzers, it has been suggested that CYP2D6 is not involved in the metabolism of methylphenidate, and that drugs that are inhibitors of CYP2D6 should not affect methylphenidate plasma concentrations (10). 

Sparteine has been used as a marker of the metabohc activity of CYP2D6 (1). Pharmacokinetic studies have shown that its metabolic oxidation exhibits genetic polymorphism and that about 6-9% of the Caucasian population are poor metabohzers. Quinidine, haloperidol, and moclobemide are all potent inhibitors of the oxidative metabohsm of sparteine (2). 

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