Effects of food intake on the bioavailability of sulpiride from AEA film-coated tablet having a pH-dependent dissolution characteristic in normal or drug-induced achlorhydric subjects.

The effect of food intake on the bioavailability of sulpiride from a commercial film-coated tablet (100 mg/T) treated with polyvinylacetal diethylaminoacetate (AEA), which remains undissolved at pH above 4 approximately 5, were investigated in four healthy male subjects in the normal state or in a drug-induced achlorhydric state. The drug was administered as a single oral 100 mg dose of sulpiride under the fasting and nonfasting state using a crossover study design. Fifteen urine samples were collected over a 48 h period following sulpiride administration to determine sulpiride concentrations by HPLC. The bioavailability was estimated from the cumulative amount excreted unchanged in urine over 48 h (Du48). When AEA film-coated tablet was taken by subjects in the normal state, the bioavailability under the fasting state differed markedly among the four subjects due to differences in gastric acidity. The effect of food intake on the bioavailability also differed markedly among the individuals, being lower in high gastric acidity subject and higher in those with low gastric acidity subjects. When AEA film-coated tablet was taken by subjects in a simulated achlorhydric state, the bioavailability under the fasting state was very poor for all four subjects and did not show inter-subject variation. With food intake, the bioavailability increased 6-fold, probably due to the more vigorous movement of the formulation in the gastrointestinal tract, since both the basal and the meal-stimulated gastric acid secretion were markedly inhibited in the simulated achlorhydric state.