Riociguat
Riociguat. Soluble guanylate cyclase (sGC) stimulator — sensitizes sGC to NO + activates the NO-independent site. Raises cGMP → pulmonary… Oral half-life 12 h.
Soluble guanylate cyclase (sGC) stimulator — sensitizes sGC to NO + activates the NO-independent site. Raises cGMP → pulmonary vasodilation. Approved for PAH + chronic thromboembolic pulmonary hypertension (CTEPH). Contraindicated with PDE5 inhibitors + nitrates (additive hypotension).
PK: F 0.94 is verbatim and, contrary to the premise this batch was audited under, IS A GENUINE MEASURED ABSOLUTE VALUE — riociguat does have an intravenous arm: "riociguat (intravenous/oral) was administered to healthy male subjects in 3 open-label, randomized, crossover studies", giving "Absolute bioavailability was 94% (95% confidence interval [CI], 83%-107%)". ka corrected 1.4 to the published 2.17 /h. The stored V of 30 L was in fact the published apparent volume of 32.3 L silently multiplied by that bioavailability — the right operation performed without recording it; 30.4 is now stored with the derivation stated, so the pairing with F is explicit rather than accidental. SMOKING STATUS IS UNRECORDED IN BOTH CITED PAPERS AND MATTERS ENORMOUSLY: clearance is 120% higher in smokers, exposure falls by at least 60%, and accumulation is minimal in smokers against roughly twofold in non-smokers. The half-life of 12 h is POPULATION-SPECIFIC — 12 h in patients against 7 h in healthy individuals — and is now cited to the paper that states it. A provenance defect is also fixed: the paper carrying the bioavailability was not in the reference list while the only listed reference carried none of the stored values.
Pharmacokinetics
- Oral — t½ 12 h · F 94% · ka 2.17 h⁻¹ · Vd 30.4 L
Sources: PMID:30997864, PMID:27096084, PMID:27162632, PMID:29086344