T. Hamaguchi et al., EFFECT OF A HIGH-FAT MEAL ON THE BIOAVAILABILITY OF PHENYTOIN IN A COMMERCIAL POWDER WITH A LARGE PARTICLE-SIZE, International journal of clinical pharmacology, therapy and toxicology, 31(7), 1993, pp. 326-330
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.