The major metabolic pathway is non-CYP metabolism, CYP-mediated formation of nitric oxide from nitrate in humans is not of clinical significance. No evidence of capacity for CYP-induction. Clinical experience points to non-porphyrinogenicity, more than 12 patient reports of tolerance supports this.

Propane-1,2,3-triol trinitrate. M= 227.1

Glyceryl trinitrate is a nitrovasodilator used in the management of angina pectoris, heart failure and myocardial infarction. Other indications include inducing hypotension and controlling hypertension during surgery. Tachycardia is a common side effect while nausea and vomiting are less common side effects.

Insignificant.

Glyceryl trinitrate 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. This reaction requires the presence of cysteine or another thiol. Glyceryl trinitrate also undergoes hydrolysis in plasma and is rapidly metabolised in the liver by glutathione-organic nitrate reductase to dinitrates and mononitrates. The dinitrates are less potent vasodilators than glyceryl trinitrate; the mononitrates may have some vasodilator activity. A high and variating plasma clearence 10-50 mL/min points to a high degree of extrahepatic metabolism. No clinical or experimental evidence of interactions with CYP-metabolism of other drugs.

In animal studies continuous administration of organic nitrates decreased hepatic P450 content and simultaneously induced hemeoxygenase (Minamiyama). Rodent experiments suggest that the biotransformation of organic nitrates may take place by direct interaction with the heme moiety of cytochrome P450 and preferentially by isocénzymes that can be induced by phenobarbital.

S.Thunell 2004: 6 patient reports (tolerated). C Andersson 2004: 5 patient reports (tolerated). Peters 2004 : some patient reports (tolerated).

Tolerated by two acute porphyria patients of unknown susceptibility (Kauppinen and Mustajoki).

Uneventful use reported in 10 patients with acute porphyria.