Robert A. Buchanan

Single daily dose of diphenylhydantoin in children

Once daily administration of the 24 hour diphenylhydantoin anticonvulsant requirement was studied in children. Each patient served as his own control by means of a crossover design. Comparison between the single and divided dose schedules failed to reveal any clinically significant differences in seizure control or drug-related toxicity. Serum levels were remarkably uniform for each patient regardless of whether the drug was administered three times per day or all at one time. No evidence of excessive drug accumulation occurred at the time of peak absorption following single daily administration. Levels obtained 24 hours after administration of the dosage were the same as those at 12 hours, indicating no tendency for subtherapeutic levels just prior to the next dose. A dose of 5 mg. per kilogram per day of diphenylhydantoin generally will produce serum concentrations of 10 μg per milliliter. The potential advantages of single daily administration are: reduced hospital nursing costs, patient convenience, and improved seizure control due to better reliability. The single daily dose must not be inadvertently forgotten.

Pharmacokinetic profile of a 300-mg extended phenytoin sodium capsule (Dilantin) formulation.

Summary: The pharmacokinetic profile of a newly developed Dilantin 300‐mg Kapseal formulation was compared with that of currently marketed Dilantin 100‐mg Kapseals in both a 300‐mg single‐dose bioequivalence study in nine healthy volunteers and a once‐daily 300‐mg multiple‐dose study in 18 patients with seizures. Results of these studies indicate the rate and extent of absorption of the 300‐mg extended phenytoin(PHT) sodium capsule formulation are similar to that of 100‐mg extended PHT sodium capsules based on PHT plasma maximum concentrations and time to achieve them (Cmsx, tmax), and area under the curve (AUC) values and the urinary excretion of total hydroxy phenylhydantoin (HPPH) in the single‐dose study and steady‐state PHT plasma Cmax, tmax, minimum plasma concentrations (Cmin), and AUC values and urinary excretion of total HPPH in the multiple‐dose study. Control of seizures in patients was equally maintained on a once‐daily 300‐mg multiple‐dosing regimen administered as either one 300‐mg extended PHT sodium capsule daily or three 100‐mg extended PHT sodium capsules daily. Therefore, 300‐mg extended PHT sodium capsules can be safely and effectively interchanged with three 100‐mg extended PHT sodium capsules in patients requiring a once‐daily 300‐mg PHT sodium dosing regimen.

Comparative Urine Concentrations of Sulfacytine, A New Sulfonamide

A new sulfonamide, sulfacytine (1-ethyl-N-sulfanilylcytosine) has a short half-life, is highly soluble throughout the usual urinary pH range, and urinary excretion is almost entirely as the free or microbiologically active form. Experimental mouse infections demonstrate a 2- to 3-fold bacteriostatic activity compared to sulfisoxazole. Plasma and urine concentrations following three dose schedules of sulfacytine (2 grams/day, 1 gram/day, 0·5 grams/day) were determined over a 7-day period by both colorimetric and microbiologic assay methods. These were compared to sulfonamide levels produced by the standard dose of sulfisoxazole (4 grams/day). Excellent agreement was found between the two methods, indicating that the colorimetric assay for free sulfacytine should accurately reflect microbiologic activity. Fifty per cent (50%) of the total daily dose given initially produces prompt levels so is the proper loading dose. By comparison to sulfisoxazole urine levels, 1 gram/day of sulfacytine appears to be the proper dose, produces urine concentrations at least 10 times the highest MIC found for sensitive microorganisms.