Phenytoin toxicity and blood levels after a large oral dose

The pharmacokinetics and side effects of a single oral 900-mg dose of phenytoin sodium were studied in six healthy men. Nine 100-mg phenytoin sodium capsules were administered with water to six fasting healthy men. Phenytoin plasma levels were measured by gas chromatography for up to 48 hours after dosing. Patients were observed and tested for gastrointestinal, cardiovascular, and neurologic side effects. Peak total (bound and free) plasma phenytoin levels were within the therapeutic range (10--20 microgram/ml) for two subjects and close (not less than 8.39 microgram/ml) for the remaining four. Peak free drug levels were 1.01--1.60 microgram/ml. Time to reach total and free peak plasma levels was long and variable (6--14 hours and 2--10 hours, respectively). Phenytoin protein binding (11.9--13.6%) was relatively stable among patients and at various plasma levels. A few mild transient side effects were noted; most occurred within two to four hours after dosing. Sinus bradycardia and a shortened PR interval were noted in two patients but did not correlate with peak plasma phenytoin levels. It appears that an oral loading dose of phenytoin sodium may be useful in ambulatory patients but further study of its side effects is recommended.