Elsevier

EAU Update Series

Volume 2, Issue 2, June 2004, Pages 56-63
EAU Update Series

Phosphodiesterase Type-5 Inhibitors: A Critical Comparative Analysis

https://doi.org/10.1016/j.euus.2004.03.007Get rights and content

Abstract

All three PDE5 inhibitors are targeting the same site of action e.g. PDE5 and this is why a quite similar efficacy and safety profile could be expected and was finally proven in many controlled studies. The efficacy as assessed by the endpoint successful intercourse with maintenance of erection (SEP3) ranges between 65 and 75% in broad-spectrum ED populations with clearly lower success-rates of 40–50% in patients with involvement of the penile nerve supply such as diabetics or patients after pelvic surgery. Generally speaking the drug-related adverse events are principally comparable except visual disturbances being more frequently reported after sildenafil and back pain/myalgia more often occurring after tadalafil.

Considering the pharmacokinetic profile tadalafil distinguishes itself from sildenafil and vardenafil by its long half-life (T1/2=17.5 h) resulting in the majority of patients in successful coitus attempts even after 112 days. As a rule of thumb the clinical efficacy of the respective PDE5 inhibitors corresponds pretty well to the 2.5–3-fold half-life time. In terms of onset of action as mirrored by the Tmax vardenafil has the shortest one (40 min) followed by vardenafil (60 min) and tadalafil (120 min) As efficacy and side-effects may be differently perceived in the same individual patient with each of the three PDE5 inhibitors it seems reasonable to grant the couples the opportunity to try all drugs sequentially.

Section snippets

The phosphodiesterase (PDE): system

Currently the PDE system includes 11 families with a total of more than 50 splice variants (isoforms) [1], [2], [3], [4], [5]. The distribution and density of PDEs varies among the different tissues. The PDEs catalyse the breakdown either of cyclic guanosine monophosphate (cGMP) or of cyclic adenosine monophosphate (cAMP), which are both second messengers with specific physiologic functions. By hydrolysing the phosphodiesterase bond of cAMP or cGMP, respectively, these second messengers are

General considerations

A head to head comparison of the different PDE5 inhibitors is only possible and provides valuable and comparable data when all the three drugs were assessed under the same conditions. The IC50 values are in particular dependent on the following parameters:

Species and tissue being investigated, enzyme assay applied, substrate concentration (should be 10-fold lower than the target PDE), pH (buffer used?) of the milieu, in which the investigations were conducted.

The differences in the respective IC

Final conclusions on the three PDE5 inhibitors sildenafil, tadalafil and vardenafil

All three PDE5 inhibitors have shown a comparable efficacy profile with success rates of 70–75% (successful intercourse with maintenance of erection) in broad-spectrum ED populations. The efficacy profile declines in special subpopulations, such as diabetic patients and those after pelvic surgical procedures to a level of between 40 and 50%, depending on the severity of the underlying etiology and the procedure (radical or BNSP RRP) being performed, respectively [12], [14], [33]. According to

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