Sildenafil-Apomorphin-Vardenafil: A comparison of the risk-and benefit profiles in the therapy of erectile dysfunction

Oral presentation

The introduction of new and effective oral treatment by means of agents with a peripheral (sildenafil and vardenafil) or central nervous (apomorphine) site of action has occurred as a result of active research on the mechanism of penile erection. Sildenafil, an orally active and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), was tested in a various numbers of studies including over 4526 patients. It produced significantly greater improvement in erectile dysfunction than placebo in all trials. There was an significant improvement in the ability to attain and maintain an erection (increased by 100% and 130% according the IIEF questionnaire).

In one study-group, overall 59% of patients treated with sildenafil were able to achieve and maintain their erections on most all occasions compared with 15% of placebo-treated patients, regardless of age, race, baseline severity and etiology of dysfunction. The most common adverse events in clinical trials with sildenafil have included vasodilatory effects, such as headache (16%), flushing (10%), dyspepsia (7%), nasal congestion (4%), abnormal vision (3%) and diarrhea (3%). Sildenafil can lead to significant decrease in systolic and diastolic blood pressure (up to 10/7 mmHg mean maximum decrease), and is absolutely contradicted in any patient undergoing any nitrite drug therapy.

Vardenafil, a new and not yet released, high selective PDE5-inhibitor, has proved his efficacy in increasing penile erection in vivo and vitro. Twenty one patients, treated with Vardenafil in a randomized, placebo-controlled, double-blind study have shown under visual, sexual stimulation a mean increase in the duration of >60% penile rigidity of 24,4 (37,2) min (single dose of 10mg or 20mg). There were 4 reports of headache, one of tiredness and nasal congestion and one of moderate flush and nasal congestion. There was a slight decrease in average recumbent systolic and diastolic blood pressure which was considered to be minor and not clinical important.

Apomorphine is a D1/D2 dopamine receptor agonist from the aprophine (non-opiate) drug class, and it is a centrally acting drug. The briefly released agent has shown its efficacy and safety in various phase III, cross-over, double-blind studies and has been administrated to over 3000 men with erectile dysfunction. Erections occurred rapidly (10-25min), and in 54% of attempts at 4mg (vs 33,8% placebo) erections suitable for intercourse were documented. Adverse effects occurred in 5% or more of all patients, using 2 or 4mg Apomorphine, including nausea (2,6%/ 20,7%), sweating (2,1%/ 9,9%), dizziness (3,3%/ 13,9%) and somnolence (2,1%/ 10,6%). The most serious adverse event was syncope, occurring in seven patients (0,8%).

Oral drugs are a well established, first-line therapy for erectile dysfunction. As more drugs are approved, it would seem that oral combination therapies should prove successful.

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