What is the strongest phosphodiesterase type 5 (PDE5) inhibitor?

From the Guidelines

Tadalafil is the strongest PDE5 inhibitor due to its longest half-life and duration of action, allowing for a longer-lasting effect compared to other medications in its class. According to the most recent and highest quality study 1, the FDA-approved oral phosphodiesterase type 5 inhibitors (PDE5i) available for management of ED in the U.S. include sildenafil, tadalafil, vardenafil, and avanafil. The study suggests that these medications have similar efficacy in the general ED population, but tadalafil's longer half-life and duration of action make it a more convenient option for patients.

Some key points to consider when prescribing tadalafil include:

• The standard starting dose for as-needed use is 10mg, and 2.5-5mg for daily use 1
• The medication works by inhibiting the PDE5 enzyme, which breaks down cyclic guanosine monophosphate (cGMP), thereby prolonging smooth muscle relaxation in the corpus cavernosum and enhancing blood flow to the penis
• Tadalafil demonstrates greater selectivity for PDE5 over other phosphodiesterase enzymes compared to other medications in its class, which may contribute to fewer off-target side effects
• Patients should take tadalafil at least 30 minutes before sexual activity, though its extended duration means timing is less critical than with other PDE5 inhibitors
• It can be taken with or without food, unlike sildenafil which may be delayed by high-fat meals

It's also important to note that the most frequently reported adverse events (AEs) in men using PDE5i are dyspepsia, headache, flushing, back pain, nasal congestion, myalgia, visual disturbance, and dizziness, with average rates similar across medications 1. However, tadalafil has been reported to have lower rates of flushing compared to other PDE5 inhibitors.

In terms of special populations, the study suggests that men with diabetes and men who are post-prostatectomy have more severe ED at baseline and respond less robustly to PDE5i 1. However, tadalafil's longer half-life and duration of action may make it a more effective option for these patients.

Overall, tadalafil's unique pharmacokinetic profile and efficacy make it the strongest PDE5 inhibitor available, and it should be considered as a first-line treatment option for patients with ED.

From the FDA Drug Label

Tadalafil is >10,000-fold more potent for PDE5 than for PDE1, PDE2, PDE4, and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs Avanafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (greater than 100-fold for PDE6; greater than 1,000-fold for PDE4, PDE8 and PDE10; greater than 5,000-fold for PDE2 and PDE7; greater than 10,000-fold for PDE1, PDE3, PDE9, and PDE11) The strongest phosphodiesterase type 5 (PDE5) inhibitor is tadalafil and avanafil, as both are highly potent and selective for PDE5, with tadalafil being >10,000-fold more potent for PDE5 than for other phosphodiesterases, and avanafil being greater than 100-fold more potent for PDE5 than for PDE6, and greater than 10,000-fold more potent for PDE5 than for PDE1, PDE3, PDE9, and PDE11 2 3. Sildenafil is also a selective inhibitor of PDE5, but its potency compared to tadalafil and avanafil is not directly stated in the provided text 4.

From the Research

Phosphodiesterase Type 5 (PDE5) Inhibitors

The strongest PDE5 inhibitor can be determined by considering several factors, including efficacy, safety, and duration of action.

• Efficacy: All PDE5 inhibitors, including sildenafil, tadalafil, and vardenafil, have been shown to be effective in treating erectile dysfunction (ED) 5, 6.
• Safety: The overall safety of PDE5 inhibitors is good, even in patients with a history of cardiovascular disease, but there is a risk of hypotension if nitrates are given concurrently 5, 7.
• Duration of action: Tadalafil has a longer duration of action, approximately 36 hours, compared to sildenafil and vardenafil, which have durations of action of about 4 hours 5, 8.

Comparison of PDE5 Inhibitors

A comparison of the three currently licensed PDE5 inhibitors, sildenafil, vardenafil, and tadalafil, shows that they have similar efficacy and toxicity profiles 9.

• Onset of action: The onset of action varies among the PDE5 inhibitors, with sildenafil and vardenafil having shorter onset times compared to tadalafil 9.
• Pharmacokinetic profile: Tadalafil has a structurally different molecular profile, which is reflected in its pharmacokinetic profile, including a longer half-life and less effect from food intake 9.

Patient Preference

Patient preference is an important aspect of ED therapy, and tadalafil seems to be the preferred drug by patients and physicians, probably due to its peculiar pharmacological profile that makes sexual intercourse more spontaneous for the patients 6.