Advances in Pharmacology and Chemotherapy Volume 7 by Silvio Garattini

By Silvio Garattini

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Similar discordant cxamples occurred for both sniolring and coffee consuniption. To determine RECENT PROURESS IN PHARMACOQENETICS 15 whether a relationship exists between these agents and levels of drug-metabolizing enzymes in humans will require much further work. Only two of the seven sets of identical twins lived in the same household; t,herefore, the close resemblance between identical twins in phenylbutazone half-lives, in antipyrine half-lives, and in dicoumarol half-lives cannot be attributed to those environmental factors, such as exposure to the same inducing agents, operating on individuals sharing the same home and meals.

The onset of nystagmus, ataxia, and mental changes in relationship to diphenylhydentoin (Dilantin) blood levels. , 1964b). Metabolism of Dilantin proceeds by parahydroxylation of one of the phenyl groups to yield 5-phenyl-5'-parahydroxyphenylhydantoin,HPPH, which is conjugated with glucuronic acid and then eliminated in urine (Butler, 1957; Woodbury and Esplin, 1959; Maynert, 1960). Kutt et al. 4 nig/kg. Their investigations established high blood levels of unchanged Dilantin and low urine levels of HPPH.

The patient feels improved, and the abnormalities noted above regress, even though administration of drug is continued. This refractory state has been attributed not to any change in the metabolism of the drug or in the reactivity of the erythrocytes, as in immunological phenomena, but rather to a change in composition of the erythrocyte population. The older, more sensitive cells with their greater relative deficiency have been eliminated. , 1954b). Non-Negro subjects with G-6-PD deficiency exhibit a similar, but more severe, clinical course.

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