MedicinePharmacologyPharmacotherapyClinical PharmacologyEpilepsyEpileptologyAntiepileptic PharmacologyAntiepileptic PharmacotherapyDrug DispositionDrug ToleranceAntiepileptic Dose AdjustmentAntiepileptic Drug DosingAntiepileptic Drug PharmacokineticsClinical Adverse EffectsDaily DosingLow-dose Tolerance
Levels of diphenylhydantoin sodium in the blood can be correlated with its clinical effects and intoxication. Therapeutic levels (10μg/ml to 15μg/ml are reached within 5 to 15 days when 300 mg are given daily; and with a larger (up to 1,000 mg) initial dose, within a few hours (orally) or minutes (intravenously). Two groups of unusual responses to commonly used doses of diphenylhydantoin have been observed. (1) Low tolerance to the drug which can be caused by congenital enzymatic deficiency, liver disease, or metabolic interference by other drugs. A reduction of the daily dose is necessary in these patients. (2) Refractoriness to diphenylhydantoin which can be caused by excessive diphenylhydantoin metabolism, deficient absorption, and unreliable diphenylhydantoin intake. An increase of dose, administering diphenylhydantoin parenterally, or supervising drug intake will provide adequate blood levels in these patients.
12
Diphenylhydantoin Metabolism, Blood Levels, and Toxicity
Henn Kutt, William Winters, R. KOKENGE et al. · Archives of Neurology · 1964 · 249 citations
Insufficient parahydroxylation as a cause of diphenylhydantoin toxicity
Henn Kutt, Michael Wolk, Rolf Scherman et al. · Neurology · 1964 · 179 citations