Effect of Food on the Oral Bioavailability of Isosorbide‐5‐Mononitrate Administered as an Extended‐Release Tablet

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Abstract
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 (IMDURTrade; 60‐mg tablets, Astra Hässle AB, Mölndal, 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 IMDURTrade; 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 IMDURTrade; 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 IMDURTrade; 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.