Effect of Diphenylhydantoin Therapy on Plasma 11-OHCS:Interference in The Effect of Dexamethasone and Metopirone

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Prolonged diphenylhydantoin (DPH) therapy is known to cause a variety of metabolic and endo-crinologic abnormalities. In an attempt to evaluate the effect of DPH on the adrenal cortical function, measurements were made of plasma levels of 11-OHCS and ACTH. In children taking DPH, base-line values remained almost normal, but these patients showed a lack of suppression of plasm 11-OHCS in response to dexamethasone and metopirone test. Serum concentrations of γ-GTP and, β-glucuronidase were raised in them.<BR>It seems likely from these studies that increas-ed metabolism of dexamethasone and metopirone due to induction of hepatic enzymes by DPH appears to have caused abnormal responses to them, as the result of subnormal inhibition of ACTH release and 11 β-hydroxylation, but there may also be delayed absorption of these drugs from the gastrointestinal tract, which is a problem open to further study.<BR>Caution is necessary, in prescribing some drugs in combination with DPH which might cause a considerably shortened plasma half-life of many drugs, and in the evaluation of results of endocrine function tests during DPH therapy.
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