The bioavailability of oral nitroglycerin

Area of Science:

• Pharmacology
• Cardiovascular Medicine
• Drug Metabolism

Background:

• Oral nitroglycerin (NTG) efficacy for angina was questioned due to early animal studies suggesting complete first-pass hepatic metabolism.
• Current understanding accepts that high oral NTG doses possess antianginal effects, possibly through metabolic saturation.
• The mechanism for oral NTG efficacy, particularly in humans, remains debated, with limited supporting experimental evidence for metabolic saturation.

Purpose of the Study:

• To determine the bioavailability of oral nitroglycerin administered via capsule and solution dosage forms.
• To investigate the pharmacokinetic profile of oral nitroglycerin and its metabolites.

Main Methods:

• Administration of oral nitroglycerin in capsule and solution forms to human subjects.
• Measurement of nitroglycerin bioavailability and plasma concentrations of its metabolites, specifically dinitrate forms.

Main Results:

• Oral doses of nitroglycerin exhibited very low bioavailability, less than 1%.
• Significantly elevated plasma concentrations of dinitrate metabolites, which have lower activity, were detected.
• These findings were derived from bioavailability studies of oral nitroglycerin preparations.

Conclusions:

• The antianginal efficacy of oral nitroglycerin preparations may be attributed to the high plasma concentrations of its dinitrate metabolites.
• This hypothesis was not directly confirmed by the presented bioavailability data but warrants further investigation.
• Further studies are needed to directly test the contribution of dinitrate metabolites to the therapeutic effect of oral nitroglycerin.