No evidence of capacity for CYP-induction. CYP-mediated formation of nitric oxide from nitrate is of no clinical significance in humans.

1,4:3,6-Dianhydro-d-glucitol 5-nitrate (Isosorbide-5-mononitrate). M =191.1.

Isosorbide 5-mononitrate is the most effective metabolite of the vasodilator isosorbide dinitrate. It is used in the long-term management of angina pectoris and heart failure. It has also been investigated in myocardial infarction. Individual dose, normal dose is 60 mg/d. Several depotpreparations are available. Common side effects are nausea and tachycardia.

No hepatic first-pass metabolism. Probably less hepatic exposure than for the tri- and di -nitrated compounds.

Unlike isosorbide dinitrate, the mononitrate does not undergo hepatic first pass metabolism. Bioavailability is nearly 100 per cent. It 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. Isosorbide mononitrate is metabolised to inactive metabolites, including isosorbide and isosorbide glucuronide. There is no human data regarding biotransformation of organic nitrates by CYP-mediated oxidation, which is contrary to that seen 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.

Rodent experiments suggest that the biotransformation of inorganic nitrates formed may take place by direct interaction with the heme moiety of cytochrome P450 and by isoenzymes induced by phenobarbital.

Thunell, patient report (n=1): tolerated. Andersson, patient report (n=2): tolerated. Peters: Experience of tolerance.

Uneventful use reported in 24 patients with acute porphyria.