Induction diphenylhydantoin

Long-term anticonvulsive therapy with diphenylhydantoin or phenobarbital is known to cause osteomalacia by influencing calcium metabolism (24,25). Alteration in the metabolism of vitamin D, presumably secondary to induction of hepatic microsomal enzymes, leads to the calcium and bone abnormalities (26). Patients on anticonvulsive therapy with phenytoin exhibit a decrease in serum 25-hydroxyvitamin D (27). Adequate dietary amounts of vitamin precursors or microsomal enzyme stimulators might prevent these effects of long-term therapy. 

J. R. Robinson and D. W. Nebert, Genetic expression of aryl hydrocarbon hydroxylase induction Presence or absence of association with zoxazolamine, diphenylhydantoin, and hexobarbital metabolism. Mol. Pharmacol. 10, 484-493 (1974). 

The potential therapeutic implications of relatively broad (phenobarbital-type) induction are obvious patients chronically treated with phenobarbital may require larger than normal doses of other drugs (diphenylhydantoin. bishydroxycoumarin) to achieve therapeutic effects. If the phenobarbital is discontinued, enzyme induction disappears and the large drug doses may precipitate toxicity. Similarly, chronic administration of a drug may induce microsomal enzymes that catalyse its own metabolism, i.e. produce auto-induction . Thus, repeated drug administration may... 

In humans, administration of o,p -DDD [l,l-dichloro-2-(4-chlorophenyl)-2-(2-chlorophenyl) ethane], phenobarbital, diphenylhydantoin, or phenylbutazone causes a marked elevation in the urinary excretion of 6 )5-hydroxycortisol presumably by accelerating the metabolism of glucocorticoids. Accordingly, treatment of animals with phenobarbital stimulates the hydroxylation by hepatic microsomes of corticosterone, deoxycorticosterone, cortisone, and cortisol, whereas 3-methylcholanthrene has negligible effect on the hydroxylation of cortisone or cortisol. The physiological consequences of this induction, however, remain obscure. 

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