Acute Porphyria Drug Database

C01DA14 - Isosorbide Mononitrate
Not porphyrinogenic
NP

Rationale
No evidence of capacity for CYP-induction. CYP-mediated formation of nitric oxide from nitrate is of no clinical significance in humans.
Chemical description
1,4:3,6-Dianhydro-d-glucitol 5-nitrate (Isosorbide-5-mononitrate). M =191.1.
Therapeutic characteristics
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.
Hepatic exposure
No hepatic first-pass metabolism. Probably less hepatic exposure than for the tri- and di -nitrated compounds.
Metabolism and pharmacokinetics
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.
Preclinical data
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.
Personal communication
Thunell, patient report (n=1): tolerated. Andersson, patient report (n=2): tolerated. Peters: Experience of tolerance.
IPNet drug reports
Uneventful use reported in 24 patients with acute porphyria.

References

  1. Scientific articles
  2. Mayer, Beretta 2008. The engima of nitroglycerin bioactivation and nitrate tolerance: views and troubles. PMID 18574453. PMID 18574453. #4793
  3. McDonald Benett 1990. Cytochrome P450 mediated biotransformation of organic nitrates. PMID 2128204. PMID 2128204. #4384
  4. Drug reference publications
  5. Martindale 2009 #3265

Similar drugs
Explore alternative drugs in similar therapeutic classes C01D / C01DA or go back.

 
© NAPOS 2024
An unhandled error has occurred. Reload 🗙