Nitroglycerin
Nitroglycerin. Prodrug → intracellular reduction (mitochondrial ALDH-2) releases nitric oxide → guanylyl cyclase activation → cGMP →… Sublingual half-life 0.1 h.
Prodrug → intracellular reduction (mitochondrial ALDH-2) releases nitric oxide → guanylyl cyclase activation → cGMP → smooth muscle relaxation. Predominantly venous dilation (decreases preload) at low doses; coronary + arteriolar dilation at higher doses. Tolerance develops within 24 h of continuous exposure — nitrate-free interval essential.
PK: ITS SOURCE WAS A NARRATIVE REVIEW WHOSE ABSTRACT CONTAINS NOT ONE NUMERAL, cited on BOTH routes and even for F:1 on the intravenous row, which no review can establish. Every value now has a real home and three of the four barely move. V 210 L was correct all along: "a large volume of distribution (approximately 3 liters/kg)" times 70 kg is 210 exactly, from an eight-subject intravenous infusion study - and because it is IV-derived it legitimately serves both routes and its pairing with an independent sublingual F is correct. t-half 0.04 h, 2.4 minutes, matched no published value and becomes 0.05 from the same sentence, "a rapid plasma half-life (approximately 3 min)". Sublingual F 0.39 becomes the verbatim absolute 0.362, "The mean bioavailability ... of sublingual nitroglycerin ... was 36.2 +/- 24.9%". THE SUBLINGUAL ROUTE IS FLIP-FLOP AND HAD NO ABSORPTION CONSTANT AT ALL: measured Tmax is "5.3 +/- 2.3 minutes", which EXCEEDS the 3-minute half-life, and the authors add that absorption "is not instantaneous and can be relatively slow, with peak times of as long as 10 minutes"; with no ka the simulator produced an instantaneous spike no study has observed, so a ka anchored to that Tmax is added and disclosed as derived. A LIVE TRAP IS RECORDED FOR FUTURE BATCHES: PMID:3105569 is a clean human study offering a 60 L volume and an 88.6% bioavailability, but its analyte is GLYCERYL-1-MONONITRATE, a metabolite.
Pharmacokinetics
- Sublingual — t½ 3 min · F 36% · ka 8 h⁻¹ · Vd 210 L
- IV — t½ 3 min · F 100% · Vd 210 L
Related compounds
- NAC — caution
Sources: PMID:3925750, PMID:3127076, PMID:6101155, PMID:3917598