Sildenafil
Sildenafil. PDE5 inhibitor — raises cGMP in cavernosal smooth muscle → erectile vasodilation. CYP3A4 substrate (DDI with all azoles, ritonavir… Oral half-life 3.7 h.
PDE5 inhibitor — raises cGMP in cavernosal smooth muscle → erectile vasodilation. CYP3A4 substrate (DDI with all azoles, ritonavir, grapefruit). Higher dose (Revatio) for pulmonary arterial hypertension.
PK: F 0.41 is verbatim from a twelve-subject crossover against a real 50 mg intravenous arm and stands. V 105 L was the exact MIDPOINT of a species-lumped "1-2 l/kg" range scaled to 70 kg; it is replaced by 127 L, the published apparent volume of 310 L multiplied by that bioavailability, with the derivation recorded. Half-life corrected to 3.7 h, and the two independent sources agree: that apparent volume with its clearance reproduces 3.67 h. ABSORPTION IS BIMODAL RATHER THAN FIRST-ORDER, so the rate is dropped rather than replaced: "the value for ka is associated with meal consumption within 2 h predose, AT ALL OTHER TIMES ka was equivalent to an instantaneous bolus administration", with 210% between-subject variability. THE EFFECT COMPARTMENT IS REMOVED — its reference is an IN-VITRO ORGAN-BATH study on human tissue strips, with no route administered and no timing of any kind, so it cannot support the note claim of a one-hour onset, and no published equilibration constant exists for this drug. The active N-desmethyl metabolite carries roughly a fifth of the activity at about half the parent exposure, so a parent-only curve understates enzyme inhibition.
Pharmacokinetics
- Oral — t½ 3.7 h · F 41% · Vd 127 L
Sources: PMID:11879259, PMID:10219969