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 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 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.
Kosoglou
T
T
Department of Clinical Pharmacology, Schering-Plough Research Institute, Schering-Plough Corp., Kenilworth, New Jersey 07033-0539, USA.
Kazierad
D J
DJ
Schentag
J J
JJ
Patrick
J E
JE
Heimark
L
L
Radwanski
E
E
Christopher
D
D
Flannery
B E
BE
Affrime
M B
MB
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D003692:Delayed-Action Preparations; D018565:Food-Drug Interactions; D005746:Gastric Emptying; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D008991:Monitoring, Physiologic
D003692:Delayed-Action Preparations; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate