EFFECT OF A HIGH-FAT MEAL ON THE BIOAVAILABILITY OF PHENYTOIN IN A COMMERCIAL POWDER WITH A LARGE PARTICLE-SIZE

The effect of a high-fat meal on the bioavailability of free acid phen ytoin (DPH) from Hydantol powder with a large particle size (mean part icle size, 190 mum) was investigated in four healthy male subjects. Th e drug was administered as a single oral 5 mg/kg dose of free acid DPH in the fasting state, with a low-fat meal, or with a high-fat meal us ing a crossover study design. Seven blood samples were collected over a 34-h period following drug administration, and the drug plasma conce ntrations were determined by GLC. In comparison with the fasting state results, the mean area under the plasma concentration-time curve up t o infinity after administration (AUC0-infinity) and the peak plasma co ncentration (C(max)) of DPH from Hydantol powder significantly increas ed about 2-fold with the intake of the high-fat meal and about 1.5-fol d with the intake of the low-fat meal. The elimination rate constant w as not significantly different among the three treatments. The increas ed bioavailability with the high-fat meal probably resulted from accel erated dissolution of the poorly soluble Hydantol powder due to the st imulation of bile flow or delay of the gastric emptying time caused by the fat intake.