Isosorbide Mononitrate
Isosorbide Mononitrate. Active metabolite of isosorbide dinitrate — bypasses hepatic first-pass nitrate conversion. Releases NO in vascular… Oral half-life 4.2 h.
Active metabolite of isosorbide dinitrate — bypasses hepatic first-pass nitrate conversion. Releases NO in vascular smooth muscle → cGMP → vasodilation; preferentially venous, reducing preload. Used for chronic stable angina + heart failure. Tolerance develops with continuous exposure → daily nitrate-free interval recommended.
PK: Straehl 1984 (PMID:6478734), healthy subjects given IV 5 mg and oral 10-20 mg, supplies three values from one study — verbatim "volume of distribution at steady state (Vd ss) was 48 l", "elimination t 1/2 was 4.15 hr" and "absolute systemic availability was 100%". Because that F is a true absolute measurement against IV, the 48 L is a true Vss and the two pair without double-counting. Corroborated independently at 48.5 L and 4.4 h (PMID:6666223). The values stored until 2026-09-06 were unsourced — the previous citation (PMID:15146932) prints no volume and no half-life value, and its "105 +/- 20%" is relative bioavailability. ka dropped, and it was not merely unsourced but contradicted: the same paper gives "absorption t 1/2 ranged from 2.5 to 5 min", i.e. 8.3-16.6 /h for the immediate-release tablet, roughly an order of magnitude faster than the stored 1.4 /h. Left unstored rather than collapsed to a midpoint. CAVEAT: nitrate tolerance develops on continuous dosing (PMID:11037739) but is PHARMACODYNAMIC — the kinetics are dose-linear and unchanged, so tolerance must never be encoded as an altered half-life or clearance.
Pharmacokinetics
- Oral — t½ 4.2 h · F 100% · Vd 48 L
Sources: PMID:15146932, PMID:6478734, PMID:11037739