Tadalafil
Tadalafil. PDE5 inhibitor with ~17h half-life — supports both on-demand and daily dosing. CYP3A4 substrate. Approved for erectile dysfunction… Oral half-life 18 h.
PDE5 inhibitor with ~17h half-life — supports both on-demand and daily dosing. CYP3A4 substrate. Approved for erectile dysfunction, BPH, and pulmonary arterial hypertension.
PK: MY PRIOR THAT THIS WOULD BE THE SIMPLE, CORRECT ONE IS REFUTED — IT HOLDS ITS GROUP LARGEST ERROR. Its citation states its own volume as apparent, in the same sentence as the clearance that convicts the record: "Mean oral clearance (CL/F) was 2.48 (1.35, 4.35) l h-1 and APPARENT volume of distribution (Vz/F) was 62.6 (39.5, 92.1) l". The stored 63 is that figure rounded, and it was paired with an F of 0.4, so the solver divided by an availability twice and asserted 6.24 L/h — 2.52x over. F 0.4 has no source anywhere: no human intravenous tadalafil formulation exists and the label states absolute bioavailability was never determined, so this is not one of the reversible class-6 judgements. Pinning F to 1 and storing the verbatim volume reproduces the published clearance to three digits, 2.479 against 2.48. THE HALF-LIFE WAS EXACTLY RIGHT ALL ALONG and is untouched, verbatim as "a mean ... t1/2 of 17.5 (11.5, 29.6) hours" — which is the whole clinical point of this drug. Its occupancy row is verified and its free-fraction correction correctly applied, because that affinity is a recombinant-enzyme value rather than a whole-blood one.
Pharmacokinetics
- Oral — t½ 17.5 h · F 100% · Vd 62.6 L
Sources: PMID:23937247