0000000000384190
AUTHOR
Ho-leung Fung
Isosorbide dinitrate: pharmacokinetics after intravenous administration.
Isosorbide dinitrate (ISDN) is an important organic nitrate found therapeutically useful in its sublingual and oral forms in various cardiovascular diseases such as angina pectoris (1) and congestive heart failure (2). Recently Distante et al. (3) showed that an intravenous infusion of this drug, at 0.021–0.083 mg/min is also effective in managing unstable angina. The availability of an intravenous dosage form of ISDN not only affords the opportunity to characterize the pharmacokinetics of this drug after this particular mode of therapy, but also gives the possibility of assessing the bio-availability of this drug after other (e.g., oral) routes of administration in patients. This latter po…
Hepatic extraction of isosorbide dinitrate in cardiac patients
Hepatic extraction of organic nitrates, including that of isosorbide dinitrate (ISDN), has been thought to be nearly complete in man but has never been directly measured. We examined the time course of plasma ISDN and metabolite concentrations in arterial and hepatic venous blood in four cardiac patients receiving an intravenous ISDN infusion. Apparent hepatic extraction of ISDN was high (90%) at the beginning of infusion but fell to about 44% 1 hr after termination of infusion. The decrease in ISDN concentration gradient across the liver correlates with an increase in plasma isosorbide-5-mononitrate concentration, but a cause-and-effect relationship resulting from metabolite inhibition can…