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Selectivity of Avanafil, a PDE5 Inhibitor for the Treatment of Erectile Dysfunction: Implications for Clinical Safety and Improved Tolerability

Wang, Run ; Burnett, Arthur L. ; Heller, Warren H. ; Omori, Kenji ; Kotera, Jun ; Kikkawa, Kohei ; Yee, Shiyin ; Day, Wesley W. ; DiDonato, Karen ; Peterson, Craig A.

Journal of sexual medicine, 2012-08, Vol.9 (8), p.2122-2129 [Periódico revisado por pares]

Malden, USA: Elsevier Inc

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Título:
Selectivity of Avanafil, a PDE5 Inhibitor for the Treatment of Erectile Dysfunction: Implications for Clinical Safety and Improved Tolerability
Autor: Wang, Run ; Burnett, Arthur L. ; Heller, Warren H. ; Omori, Kenji ; Kotera, Jun ; Kikkawa, Kohei ; Yee, Shiyin ; Day, Wesley W. ; DiDonato, Karen ; Peterson, Craig A.
Assuntos: Adverse Events ; Avanafil ; Carbolines - adverse effects ; Carbolines - therapeutic use ; Clinical trials ; Congress ; Drugs ; Erectile Dysfunction ; Erectile Dysfunction - drug therapy ; Humans ; Imidazoles - adverse effects ; Imidazoles - therapeutic use ; Inhibition ; Male ; Muscles ; Musculoskeletal system ; PDE5 Inhibitor ; Penile Erection - drug effects ; Phosphodiesterase 5 Inhibitors - adverse effects ; Phosphodiesterase 5 Inhibitors - therapeutic use ; Piperazines - adverse effects ; Piperazines - therapeutic use ; Purines - adverse effects ; Purines - therapeutic use ; Pyrimidines - adverse effects ; Pyrimidines - therapeutic use ; Randomized Controlled Trials as Topic ; Reviews ; Selectivity ; Side effects ; Sildenafil Citrate ; Sulfones - adverse effects ; Sulfones - therapeutic use ; Tadalafil ; Triazines - adverse effects ; Triazines - therapeutic use ; Vardenafil Dihydrochloride
É parte de: Journal of sexual medicine, 2012-08, Vol.9 (8), p.2122-2129
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Descrição: Phosphodiesterase type 5 (PDE5) inhibitors are indicated for the treatment of erectile dysfunction (ED); however, they can also inhibit other PDE isozymes, affecting their target tissues (e.g., PDE1: heart; PDE6: retina; and PDE11: skeletal muscle), which in some cases can cause unwanted side effects and therapy discontinuation. Data from in vitro studies showed that avanafil, a PDE5 inhibitor for the treatment of ED, exhibited strong selectivity toward PDE5 and against all other PDE isozymes. To review the inhibitory effects of avanafil for PDE isozymes compared with those of sildenafil, tadalafil, and vardenafil and to discuss these results within the context of clinical trial safety observations. Review of in vitro selectivity data for avanafil (published primary data from a peer‐reviewed journal and scientific congress abstracts); PubMed search for pertinent publications on PDE5 inhibitor safety data; and review of published articles and abstracts from avanafil phase 1, 2, and 3 clinical trials. A low incidence of some PDE‐related adverse events may be reflected by the high selectivity of avanafil against non‐PDE5 isozymes. Avanafil is highly selective toward PDE5 and against all other PDE isozymes tested. Lower selectivity against PDE1, PDE6, and PDE11 is consistent with results from randomized, placebo‐controlled, phase 3 trials in which musculoskeletal and hemodynamic adverse events were reported in <2% of patients and no color vision‐related abnormalities were reported with avanafil doses up to 200 mg once daily. Data suggest that avanafil may confer a safety benefit, in terms of a lower incidence of specific adverse events, by virtue of its high specificity to PDE5 and its overall selectivity against other PDE isozymes. Wang R, Burnett AL, Heller WH, Omori K, Kotera J, Kikkawa K, Yee S, Day WW, DiDonato K, and Peterson CA. Selectivity of avanafil, a PDE5 inhibitor for the treatment of erectile dysfunction: Implications for clinical safety and improved tolerability. J Sex Med 2012;9:2122–2129.
Editor: Malden, USA: Elsevier Inc
Idioma: Inglês

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Selectivity of Avanafil, a PDE5 Inhibitor for the Treatment of Erectile Dysfunction: Implications for Clinical Safety and Improved Tolerability

Wang, Run ; Burnett, Arthur L. ; Heller, Warren H. ; Omori, Kenji ; Kotera, Jun ; Kikkawa, Kohei ; Yee, Shiyin ; Day, Wesley W. ; DiDonato, Karen ; Peterson, Craig A.

Malden, USA: Elsevier Inc

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