Sildenafil is the original PDE5 inhibitor and remains the most widely recognized erectile dysfunction medication worldwide. For the PED community, it provides on-demand sexual performance support during cycles that impair function, as well as acute pre-workout vasodilation for enhanced muscle pumps. Its shorter duration of action (4-6 hours) compared to tadalafil makes it better suited for as-needed use rather than daily dosing. Sildenafil is also used at high doses (20mg TID as Revatio) for pulmonary arterial hypertension, demonstrating its potent vasodilatory properties.
Notes
Sildenafil was FDA-approved in 1998 as the first oral PDE5 inhibitor (Viagra). It was originally being developed for angina and pulmonary hypertension when researchers noticed the erectile function side effect. The Revatio formulation (20mg TID) is used for pulmonary arterial hypertension. For bodybuilders, sildenafil is primarily an as-needed tool — used acutely for sexual encounters or pre-workout — while tadalafil is preferred for continuous daily coverage due to its longer half-life and lack of food interaction.
Sildenafil selectively inhibits PDE5, the enzyme that breaks down cGMP in smooth muscle cells. When a man is sexually stimulated, nitric oxide (NO) is released in the corpus cavernosum, activating guanylyl cyclase to produce cGMP. cGMP relaxes smooth muscle, allowing blood to fill the penile sinusoids and produce an erection. PDE5 normally degrades cGMP to terminate the erection. Sildenafil inhibits this degradation, allowing cGMP to accumulate and prolonging the vasodilatory response. Importantly, sildenafil does not create arousal — it enhances the physiological response to existing sexual stimulation. Sildenafil also inhibits PDE6 in the retina, which causes the characteristic blue-tinted vision side effect.
Oral bioavailability is approximately 40%. High-fat meals reduce Cmax by 29% and delay Tmax by 60 minutes — this is a significant food interaction. Peak plasma concentration in 30-120 minutes (median 60 minutes) on an empty stomach. Highly protein-bound (96%). Metabolized primarily by CYP3A4 (major) and CYP2C9 (minor) to an active N-desmethyl metabolite with approximately 50% the potency of sildenafil. Terminal half-life of 3-5 hours. The active metabolite has a half-life of approximately 4 hours.
Typical Dose
Erectile function (as-needed): 50-100mg taken 30-60 minutes before sexual activity. Pre-workout pump enhancement: 25-50mg taken 45-60 minutes before training. Low-dose daily: 25mg/day (less common than daily tadalafil but used by some). During PCT for sexual function support: 50-100mg as needed.
Frequency
As-needed basis. Effect onset 30-60 minutes. Duration 4-6 hours. Not ideal for daily use compared to tadalafil due to shorter half-life.
Administration
Oral tablet. Best taken on an empty stomach or with a light, low-fat meal — high-fat meals significantly delay absorption and reduce peak concentration.
Half-Life
3-5 hours
Contraindications