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Drug Insight: oral phosphodiesterase type 5 inhibitors for erectile dysfunction

Nature Clinical Practice Urology volume 2, pages 239–247 (2005)Cite this article

Abstract

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men. At present, first-line oral pharmacotherapy for most patients with ED is a phosphodiesterase type 5 (PDE-5) inhibitor, of which three are currently available worldwide. Sildenafil (Viagra®, Pfizer) has a very satisfactory efficacy–safety profile in all patient categories. The first PDE-5 inhibitor to reach the market, it is now the most widely prescribed oral agent for ED. Tadalafil (Cialis®, Lilly ICOS) and vardenafil (Levitra®, Bayer/GlaxoSmithKline) were introduced to the European Union and the US in 2003 and 2004, respectively. These three PDE-5 inhibitors share many characteristics, but each has unique features. This review describes the chemical, pharmacologic and clinical features of sildenafil, vardenafil and tadalafil as oral first-line treatments for ED. First, we describe the physiology of penile erection and PDE-5 inhibitor pharmacology, including chemistry, PDE selectivity, pharmacokinetics, and possible drug interactions. We then summarize data on the efficacy and safety profiles of the three PDE-5 inhibitors for the treatment of ED in the general population, in patients with diabetes mellitus and in men that have undergone bilateral nerve-sparing retropubic radical prostatectomy.

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Author information

Authors and Affiliations

  1. the Department of Urology at Università Vita Salute San Raffaele, Milan, Italy

    Alberto Briganti, Andrea Salonia, Andrea Gallina, Antonino Saccà, Patrizio Rigatti & Francesco Montorsi

  2. the Department of Cardiology at the University of Milan School of Medicine, Milan, Italy

    Piero Montorsi

Authors
  1. Alberto Briganti
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  2. Andrea Salonia
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  3. Andrea Gallina
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  4. Antonino Saccà
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  5. Piero Montorsi
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  7. Francesco Montorsi
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Correspondence to Francesco Montorsi.

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Glossary

CYTOCHROME P450S

A superfamily of heme proteins, most of which catalyse incorporation of a single atom of oxygen into a substrate

AUC

The area under the curve analysis is an empirical quantity that evaluates a ranking function with respect to a particular data sequence

50% INHIBITORY CONCENTRATION (IC50)

The molar concentration of an agonist necessary to produce 50% of the maximum possible inhibitory response for that agonist

INTERNATIONAL INDEX OF ERECTILE FUNCTION (IIEF]

A 15-item self-administered questionnaire to assess erectile function in the previous 4 weeks, used to detect treatment-related changes

NUMBER NEEDED TO TREAT (NNT)

Number of patients who must be subjected to an intervention before the outcome of interest occurs (e.g. number needed to prevent an adverse outcome)

NUMBER NEEDED TO HARM

The number of patients that need to be treated to harm one patient

IIEF QUESTION 3

“When you attempted sexual intercourse, how often were you able to penetrate (enter) your partner?”

IIEF QUESTION 4

“During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner?”

IIEF GLOBAL EFFICACY QUESTION

“Has the treatment you have been taking over the past study interval improved your erections?”

SEXUAL ENCOUNTER PROFILE (SEP) QUESTION 2

“Were you able to insert your penis into your partner's vagina?”

SEXUAL ENCOUNTER PROFILE (SEP) QUESTION 3

“Did your erections last enough to have successful intercourse?”

ST-SEGMENT DEPRESSION

At least 0.1 mV horizontal or downsloping ST-segment depression of the ECG compared with the baseline ST level for at least 1 min, separated from another episode by at least 1 min

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Briganti, A., Salonia, A., Gallina, A. et al. Drug Insight: oral phosphodiesterase type 5 inhibitors for erectile dysfunction. Nat Rev Urol 2, 239–247 (2005). https://doi.org/10.1038/ncpuro0186

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