Rapid and slow release phenytoin in epileptic patients at steady state: comparative plasma levels and toxicity.

Phenytoin plasma level and toxicity data were compared in a three-way crossover study performed in 18 patients at steady state. Formulations compared were a rapid and a slow release capsule and an oral solution. Plasma concentration-time integrals and maximum plasma phenytoin levels were significantly greater for the rapid release capsule and solution than for the slow release capsule. The incidence of nystagmus and toxicity did not differ for the three treatments, but the occurrence of mental symptoms was more frequent for the oral solution, possibly because of the solvent used in this formulation.

Rapid and slow release phenytoin in epileptic patients at steady state: assessment of relative bioavailability utilizing Michaelis-Menten parameters.

The bioavailability of phenytoin from rapid release capsule and oral solution formulations relative to that of a slow release capsule formulation was assessed in five patients who had participated in a three-way crossover study performed at steady state. The subjects then underwent dosage adjustment utilizing the slow release formulation, and estimates of their Michaelis-Menten parameters thus obtained were utilized in calculating the relative bioavailabilities. In addition, expected changes in steady-state plasma phenytoin concentrations were calculated assuming initial levels of 15 mg/liter, with increases and decreases in bioavailability of 10%. The consequences of such alterations in the extent of phenytoin absorption or average content of the dosage form may be clinically significant, particularly where the initial phenytoin level is equal to or greater than the patient's operative Km.