Antiischemic effects of a newly developed capsule containing 120 mg isosorbide dinitrate in sustained release form

Abstract

It is well established that constant nitrate plasma levels, as generated by “q 8 hrs” ingestions as well as by transdermal applications, induce an attenuation or even complete loss of the antiischemic effects during chronic treatment due to the development of tolerance.1–3 As we have shown first in 1983, the once-daily ingestion of isosorbide dinitrate with its waxing and waning plasma levels prevents the development of tolerance during chronic treatment.1,2 However, the duration of action of that intermittent dosage regimen was rather limited and inconsistent. To extend the duration of the antiischemic effects of a once-daily dosage, a new formulation, i.e., a capsule containing 120 mg of isosorbide dinitrate in slow release form, was created. This study assessed this newly developed capsule with regard to the antiischemic effects at 2 hours, 6 hours and 12 hours after its ingestion. Additionally, the plasma levels of isosorbide dinitrate and its active metabolites isosorbide-2-mononitrate and isosorbide-5-mononitrate were determined.