PDE5 inhibitors: efficiency, safety compare perspectives

Similar to sildenafil (Viagra pills Australia), both vardenafil and tadalafil are both potent PDE5 inhibitors. They all have a contraindication in men receiving organic nitrates. The biochemical potency of a PDE5 inhibitor is described by its IC50—the concentration of the enzyme necessary to inhibit 50% of the enzyme activity. The IC50 of all three PDE5 inhibitors is within the same range of 1–10 nM. However, vardenafil appears to be more potent within this range. Regardless, the three appear to have equal clinical efficacy. In addition, sildenafil and vardenafil appear to demonstrate some mild PDE6 inhibitory properties at high doses. This is associated with mild transient visual disturbances and, at least in the case of sildenafil, is not associated with any significant acute or chronic effect in men with normal visual function or in men with macular degeneration, treated glaucoma, or non-proliferative diabetic retinopathy. Tadalafil is a PDE11 inhibitor. PDE11 is found in the anterior pituitary, testes, prostate and heart. It is unresolved as to whether PDE11 inhibition will cause alterations in sperm function or, more importantly, whether it will increase inotropism and myocardial oxygen consumption.


Vardenafil is a potent selective PDE5 inhibitor. It is contraindicated in men taking organic nitrates. A North American, phase 3, multicenter, randomized, double-blind, placebo-controlled, four-arm, parallelgroup comparison of vardenafil 5, 10, and 20 mg vs placebo was recently published. In this study, similar to sildenafil, patients were instructed to take study medication approx 1 h before intended sexual intercourse. Vardenafil is both chemically and pharmacologically nearly identical to sildenafil. It has a similar pharmacokinetic, efficacy and safety profile. This study consisted of 805 men at 54 study centers who completed baseline evaluations and were randomized to treatment with either placebo (n = 197) or vardenafil 5 mg (n = 205), 10 mg (n = 206), or 20 mg (n = 197). Over the course of 26 wk of therapy, 37% of all patients (297 of 805) discontinued. Of patients randomized to placebo, 54% discontinued, most commonly because of insufficient therapeutic effect (20%). Of patients randomized to vardenafil, 31% discontinued, most commonly because they were lost to follow-up (9%). Overall, patients were diagnosed with ED a mean of 3.6 yr before screening and experienced symptoms of ED an average of 2.3 yr before the clinical diagnosis was made. Sildenafil had been used previously by 71% , all of whom experienced improved erections during this treatment. Only 15 of 256 screening failures were caused by failure to respond to sildenafil. The following were observed medical conditions at screening:
 hypertension (37%),
 pure hypercholesterolemia (24%),
 type 2 diabetes.

Successful penetration increased from 40.9% at baseline to 80.5% at wk 12, and the ability to maintain an erection for successful intercourse increased from 14.7% at baseline to 64.5% at wk 12. All groups showed continued improvements vs baseline throughout the 26-wk treatment period, and differences between scores for placebo-treated patients and those randomized to vardenafil remained significant at all time points.


In general, treatment with vardenafil was well tolerated Most of the side effects were mild or moderate in intensity.

The most commonly reported side effects associated with 20 mg vardenafil are:
 Headaches (18%), and flushing.
 Visual changes occurred in less than 2% of patients.
 There was a trend toward a greater decrease in blood pressure with vardenafil 10 mg and 20 mg than with placebo and vardenafil 5 mg. Nevertheless, mean blood pressure decreases in patients taking 5, 10, or 20 mg vardenafil were small, ranging from –3.6 to –6.6 mm Hg for supine SBP, –3.5 to –6.5 mm Hg for standing SBP, –3.5 to –4.8 mm Hg for supine DBP, and –2.1 to –4.5 mm Hg for standing DBP.
 It is expected, because of its chemical and pharmacological similarity to sildenafil, vardenafil will have similar cardiovascular effects, particularly with respect to central hemodynamics.