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 rate on the oral bioavailability of a isosoribide-5-mononitrate (5-ISMN) controlled-release tablet formulation (IMDUR 60-mg tablets, Astra Hassle AB, Molndal, Sweden) relative to an oral solution in 18 healthy men. Gastric emptying was monitored by radiotelemetry using the Heidelberg capsule technique. After administration of the 5-ISMN 60-mg solution, absorption was rapid with mean peak plasma 5-ISMN concentrations of 1533 ng/mL achieved in less than 1 hour. In contrast, after administration of IMDUR 60-mg tablets, the drug was more slowly absorbed, reaching mean peak plasma concentrations of 541 ng/mL in 3 to 4 hours. The bioavailability of 5-ISMN from IMDUR tablets under fasted 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 tablets under fasted conditions was 68 minutes, and in the presence of food was increased to 478 minutes, with 9 of the 18 subjects having gastric emptying delayed for at least 600 minutes. We conclude that in the presence of food, gastric emptying time is considerably increased causing a delay in drug absorption and a slight increase in the bioavailability of 5-ISMN from this controlled-release tablet formulation, however this effect is not clinically relevant.
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