1982 Volume 102 Issue 12 Pages 1162-1170
Effects of diet intake on the bioavailability of experimental tablets and suspension containing bisbentiamine, a lipophylic thiamine prodrug with pH-dependent solubility, were systematically investigated by measuring urinary thiamine excretion in man. A standard breakfast as well as high carbohydrate, high protein and high fat meals were given at fixed time of 9 : 00 A.M., and the dosing time of bisbentiamine varied in relation to the breakfast time otherwise specified. Approximately in common with the two dosage forms, the extent and the rate of bioavailability decreased significantly on preprandial administration and also tended to decrease in postprandial conditions as compared to that of between meals and fasted conditions. The high protein diet decreased greatly and the high fat meal increased slightly the bioavailability. A decrease in the bioavailability was not always accompanied with the delay in gastric emptying in postprandial conditions estimated by maximum urinary excretion time. Good correlations were found between bioavailability and the gastric acidity determined by concomitant administration of commercial diagnostic agent for gastric secretion. Extreme inter-individual variation was noted in the bioavailability of tablets administered in fasted conditions, though situation was greatly different with formulation of tablets. On the basis of the above findings, possible interaction of pharmaceutical and physiological factors affecting bioavailability of bisbentiamine are discussed.
