Tadalafil Improved Erectile Function at Twenty‐Four and Thirty‐Six Hours After Dosing in Men With Erectile Dysfunction: US Trial

Abstract

ABSTRACT:In a previous study assessing tadalafil for the treatment of erectile dysfunction (ED), tadalafil 20 mg was shown to improve erectile function for up to 36 hours vs placebo. This study sought to demonstrate the effectiveness of both 10-and 20-mg tadalafil vs placebo at 2 prespecified assigned times of 24 and 36 hours postdosing. This double-blind, placebo-controlled, parallel-group study randomized 483 men with ED into 6 groups according to a combination of treatment (placebo, tadalafil 10 or 20 mg) and assigned time (24 or 36 hours) for intercourse attempts. Patients were stratified by baseline ED severity based on Erectile Function Domain scores. The study had 4 phases: a 4-week run-in (no ED medication taken); a 2-to 4-week equilibration (dosing as needed); a 4-to 6-week assessment; and a 6-month open-label extension. During the assessment phase, men took a total of 4 doses of study medication, each dose separated by more than or equal to 7 days. Efficacy was measured as the mean per-patient percentage of successful intercourse attempts (Sexual Encounter Profile Diary Question 3: SEP3) during the assessment phase. Men taking either 10-or 20-mg tadalafil had a significant increase in SEP3 from baseline scores vs placebo at both 24 hours (P ϭ .038 and Ͻ.001 for 10 and 20 mg, respectively) and 36 hours (P Ͻ .001 for both doses) postdose. The mean per-patient percentages of successful intercourse attempts for the 24-hour time point were 41.8%, 55.8%, and 67.3% for placebo and tadalafil 10 and 20 mg, respectively; for the 36-hour time point, the mean per-patient percentages were 32.8%, 56.2%, and 61.9% for placebo and tadalafil 10 and 20 mg, respectively. The most common treatment-emergent adverse events were headache, back pain, dyspepsia, and nasopharyngitis. Both 10-and 20-mg tadalafil improved erectile function for up to 36 hours postdosing in men with ED of varied severity.

cGMP-Dependent Protein Kinases and cGMP Phosphodiesterases in Nitric Oxide and cGMP Action

“…In many men treated with PDE5 inhibitors (sildenafil or tadalafil) for relief of erectile dysfunction, improvement of the erectile response persists beyond the time required for plasma clearance of the drugs (t 1/2 values of 4 and 18 h, respectively) to subtherapeutic levels (Porst et al, 2003;Moncada et al, 2004;Young et al, 2005;Shabsigh et al, 2006). This suggests that sustained high level of the inhibitors in plasma is not required for continued therapeutic efficacy.…”

Molecular mechanisms that could contribute to prolonged effectiveness of PDE5 inhibitors to improve erectile function

“…There are now numerous reports that many individuals who use PDE5 inhibitor medications experience an improvement in the erectile response long after the plasma level of the respective drug is below what is considered to be a therapeutic level. [20][21][22][23][24] In this report, we will discuss molecular mechanisms that could account for prolonged action of PDE5 inhibitors.…”

Sildenafil citrate efficacy 8 h postdose in men with mild to moderate erectile dysfunction

“…23 The mean PPP of successful intercourse at the end of 4-6 weeks of double-blind, placebocontrolled treatment with tadalafil 20 mg was 77.4% (mild ED) and 85.9% (moderate ED) at 24 h postdose and was 75.7% (mild ED) and 57.8% (moderate ED) at 36 h postdose. 24 Thus, all phosphodiesterase type 5 inhibitors currently marketed for the treatment of ED enable successful intercourse for at least twice as long as the t 1/2 .…”