DILATRATE-SR- isosorbide dinitrate capsule, extended release
Schwartz Pharma
Description
Isosorbide dinitrate (ISDN) is 1,4:3,6-dianhydro-D-glucitol 2,5 dinitrate, an organic nitrate whose structural formula is
Image from Drug Label Content
and whose molecular weight is 236.14. The organic nitrates are vasodilators, active on both arteries and veins. Each dilatrate�-SR sustained release capsule contains 40 mg of isosorbide dinitrate, in a micro-dialysis delivery system that causes the active drug to be released over an extended period. Each capsule also contains ethylcellulose, lactose, pharmaceutical glaze, starch, sucrose and talc. The capsule shells contain D&C Red 33, D&C Yellow 10, gelatin and titanium dioxide.
Clinical Pharmacology
The principal pharmacological action of isosorbide dinitrate is relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload). Dilatation of the coronary arteries also occurs. The relative importance of preload reduction, afterload reduction, and coronary dilatation remains undefined.
Dosing regimens for most chronically used drugs are designed to provide plasma concentrations that are continuously greater than a minimally effective concentration. This strategy is inappropriate for organic nitrates. Several well-controlled clinical trials have used exercise testing to assess the antianginal efficacy of continuously-delivered nitrates. In the large majority of these trials, active agents were no more effective than placebo after 24 hours (or less) of continuous therapy. Attempts to overcome nitrate tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours has their antianginal efficacy been restored.
Pharmacokinetics
The kinetics of absorption of isosorbide dinitrate from dilatrate�-SR sustained release capsules have not been well studied. Studies of immediate-release formulations of ISDN have found highly variable bioavailability(10 to 90%), with extensive first-pass metabolism in the liver. Most such studies have observed progressive increases in bioavailability during chronic therapy; it is not known whether similar increases in bioavailability appear during the course of chronic therapy with dilatrate�-SR sustained release capsules.
