Hydralazine
Hydralazine. Direct arterial vasodilator — likely via NO pathway + IP3 / Ca²⁺ inhibition in vascular smooth muscle. Used as adjunct in HFrEF… Oral half-life 0.9 h.
Direct arterial vasodilator — likely via NO pathway + IP3 / Ca²⁺ inhibition in vascular smooth muscle. Used as adjunct in HFrEF (the BiDil combination with isosorbide dinitrate showed mortality reduction in self-identified Black patients). Drug-induced lupus is the classic adverse effect.
PK: the stored 3 h contradicts its own citation, which says 4 to 6 h — AND BOTH ARE WRONG. The companion intravenous study by the same group (PMID:7438689) gives "terminal half-life, t1/2 (53.7 min, harmonic mean)" and explains the discrepancy: "Reports based on nonselective assay methods have underestimated CLT, Vd ss, and Vd area and have overestimated the t1/2 of hydralazine", because the drug circulates largely as a hydrazone whose own half-life is 239 min. V 408 L is that paper Vd,area of 5.83 L/kg, chosen over its steady-state 1.83 L/kg because it is the one consistent with the terminal half-life and the stated clearance. F 0.313 IS A SINGLE PHENOTYPE STRATUM, NOT A POPULATION VALUE, and is now labelled as such: the same sentence gives 9.5% and 6.6% for fast acetylators against 31.3% and 39.3% for slow, a six-fold split, and first-pass is additionally SATURABLE so bioavailability rises with dose. The slow-acetylator single-dose arm is stored as the higher-exposure case. The intramuscular route is removed: no cited paper supports it.
Pharmacokinetics
- Oral — t½ 54 min · F 31% · Vd 408 L
- IV — t½ 54 min · F 100% · Vd 408 L
Sources: PMID:7438695, PMID:7438689, PMID:7381691