Pharmacokinetics of oral isosorbide-5-mononitrate in patients with ischemic heart failure.
This study compared the pharmacokinetics of orally administered isosorbide-5-mononitrate (20 mg) in patients with and without signs of ischemic heart failure after acute myocardial infarction. The central venous pressure was used as a parameter of global myocardial function and to separate 17 patients into two groups with normal (group I: CVP less than 6 cmH2O; Killip class I; n = 9) and elevated (group II: CVP greater than or equal to 6 cmH2O; Killip class II-III; n = 8) pressure. As compared to subjects with normal CVP patients with hemodynamic impairment showed a markedly lower peak concentration of isosorbide-5-mononitrate levels (475 +/- 32 vs 663 +/- 38 ngml-1; p less than 0.01; mean +/- SEM) which occurred delayed (32 +/- 6 vs 55 +/- 9 s; p less than 0.05). Reduced cardiac function also resulted in a prolonged elimination of isosorbide-5-mononitrate as was suggested by the diminished elimination rate constant (0.14 +/- 0.01 vs 0.18 +/- 0.01 h-1; p less than 0.05). Thus, in patients with ischemic heart failure cardiac performance influences both the absorption and apparent elimination phase of oral isosorbide-5-mononitrate.