Effect of antacids on the bioavailability of diflunisal in the fasting and postprandial states.
Diflunisal is long-acting salicylate derivative. We examined the effect of single concomitant doses of three antacids on diflunisal bioavailability under fasting or fed conditions (30 min after finishing a standard meal). With the use of an open, randomized, and balanced design, one 250-mg diflunisal tablet was given to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area uiven to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area uiven to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area under the time curve (AUC), peak plasma concentrations, and 0-to 96-hr urinary excretion were determined. Food (alone) decreased peak plasma concentrations by 16% (P less than 0.05) but did not affect AUC or urinary excretion. Under fasting conditions, aluminum hydroxide reduced AUC by 26% (P less than 0.01), peak plasma concentrations by 46% (P less than 0.01), and urinary excretion by 14% (P less than 0.05). Magenisuum hydroxide suspension (in the fasting state) increased the early plasma concentrations (by 130% at 0.5 hr and 64% at 1 hr, P less than 0.05) and increased AUC by 10% (P less than 0.05) but had no effect on urinary excretion. In the fed state neither aluminum hydroxide nor the aluminum hydroxide/magnesium hydroxide mixture had any detectable effect.
D000328:Adult; D000536:Aluminum Hydroxide / Q000378:metabolism; D000863:Antacids / Q000494:pharmacology*; D001682:Biological Availability; D002986:Clinical Trials as Topic; D004061:Diflunisal / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005215:Fasting; D005502:Food; D005782:Gels; D006801:Humans; D008276:Magnesium Hydroxide / Q000378:metabolism; D008297:Male; D012459:Salicylates / Q000378:metabolism*; D013535:Suspensions; D013997:Time Factors
D000863:Antacids; D005782:Gels; D012459:Salicylates; D013535:Suspensions; D000536:Aluminum Hydroxide; D004061:Diflunisal; D008276:Magnesium Hydroxide