EFFECT OF FOOD ON THE ORAL BIOAVAILABILITY OF ISOSORBIDE-5-MONONITRATE ADMINISTERED AS AN EXTENDED-RELEASE TABLET

We evaluated the effect of a high-fat breakfast and gastric emptying r ate on the oral bioavailability of a isosoribide-5-mononitrate (5-ISMN ) controlled-release tablet formulation (IMDUR(TM) 60-mg tablets, Astr a Hassle AB, Molndal, Sweden) relative to an oral solution in 18 healt hy men. Gastric emptying was monitored by radiotelemetry using the Hei delberg capsule technique.(6-9) After administration of the 5-ISMN 60- mg solution, absorption was rapid with mean peak plasma 5-ISMN concent rations of 1533 ng/mL achieved in less than 1 hour. In contrast, after administration of IMDUR(TM) 60-mg tablets, the drug was more slowly a bsorbed, reaching mean peak plasma concentrations of 541 ng/mL in 3 to 4 hours. The bioavailability of 5-ISMN from IMDUR(TM) tablets under f asted conditions was approximately 78% relative to the solution; and, in the presence of food, the bioavailability was slightly increased to 86% (P = .057). The mean gastric residence time of IMDUR(TM) tablets under fasted conditions was 68 minutes, and in the presence of food wa s increased to 478 minutes, with 9 of the 18 subjects having gastric e mptying delayed for at least 600 minutes. We conclude that in the pres ence of food, gastric emptying time is considerably increased causing a delay in drug absorption and a slight increase in the bioavailabilit y of 5-ISMN from this controlled-release tablet formulation, however t his effect is not clinically relevant.