No evidence of capacity for CYP-induction. CYP-mediated formation of nitric oxide from nitrate is of no clinical significance in humans. Three patient reports (N=3) supports the clinical evidence of non-porphyrogenicity.

1,4:3,6-Dianhydro-d-glucitol 2,5-dinitrate. Non-cyclic organic dinitrate. M= 236.1.

Isosorbide dinitrate is a vasodilator with general properties similar to those of glyceryl trinitrate. It is used in the management of angina pectoris and of heart failure. It has also been investigated in myocardial infarction. Peroral administration, tablets (5, 10, 20, 40 mg) masticated (in acute angina) or swallowed. Individual dose and duration of therapy. Nausea and tachycardia are common side effects.

Insignificant.

Isosorbide dinitrate is widely distributed with a large apparent volume of distribution. It is taken up by smooth muscle cells of blood vessels and the nitrate group is cleaved to inorganic nitrite and then to nitric oxide. It is also rapidly metabolised in the liver to the major active metabolites isosorbide 2-mononitrate and isosorbide 5-mononitrate. No human data regarding avenues of biotransformation of organic nitrates by CYP-mediated oxidation, like in rats. It can be excluded that activation of PXR/CAR should be accomplished by an inorganic nitrogen compound, and that it should be accompanied by induction of ALAS1. No interferences with CYP-metabolism of other drugs observed.

Rodent experiments suggest that the biotransformation of inrganic nitrates formed may take place by direct interaction with the heme moiety of cytochrome P450 and by isoenzymes induced by phenobarbital. McDonald Benett 1990. Cytochrome P450 mediated biotransformation of organic nitrates. PMID 2128204.

Andersson 2004: 1 patient report (tolerated).

Kauppinen and Mustajoki 1992. Prognosis of acute porphyria: Occurrence of acute attacks, precipitating factors, and assocciated diseases. Medicine 1992; 71, 1-13. Two patient reports (tolerated n=2).

Uneventful use reported in 1 patient with acute porphyria.