The renal handling of diphenylhydantoin and 5‐(p‐hydroxyphenyl)‐5‐phenylhydantoin

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Abstract
The renal clearances of diphenylhydantoin (DPH) and its maior metabolite, 5‐(p‐hydroxyphenyl)‐5‐phenylhydantoin (HPPH) have been measured in groups of 16 and 14 ambulant epileptic patients, respectively. All patients had normal renal function (creatinine clearances, 83 to 148 ml per minute), and were taking oral diphenylhydantoin sodium in doses of 300 to 500 mg per day. DPH clearance (3 to 23 ml per minute, depending on urine flow rate) was considerably less than that expected for inulin, and it seems probable that DPH undergoes net resorption in its passage through the kidney. HPPH clearance (76 to 420 ml per minute depending on urine flow rate) exceeded expected inulin clearance if urine flow rates were sufficiently high, allowing the Stlggestion that net secretion of HPPH occurs during its passage through the nephron. Although the clearances of both compounds increase with urine flow rate, it is concluded that neither oliguria nor polyuria would be likely to greatly influence plasma DPH concentration in the short term, making dosage adiustment in these two circumstances unnecessary, at least as a matter of urgency.

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