Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy. PURPOSE: More than one-third of men may experience erectile dysfunction (ED) after nerve sparing radical retropubic prostatectomy. The efficacy and safety of vardenafil, a potent, selective, phosphodiesterase 5 inhibitor, was assessed for the treatment of ED after radical prostatectomy. MATERIALS AND METHODS: In this double-blind study 440 men with ED after nerve sparing radical prostatectomy were randomized to take placebo, or 10 or 20 mg vardenafil. Efficacy was measured after 12 weeks using the erectile function domain of the International Index of Erectile Function, diary questions measuring vaginal penetration and intercourse success rates, and a global assessment question (GAQ) on erection. RESULTS: Of the intent to treat population 70% had severe ED (erectile function less than 11) at baseline. After 12 weeks both vardenafil doses were significantly superior to placebo (p
Efficacy and tolerability of vardenafil for treatment of erectile dysfunction in patient subgroups.
Efficacy and tolerability of vardenafil for treatment of erectile dysfunction in patient subgroups. OBJECTIVES: To assess whether vardenafil would improve erectile function irrespective of etiology, baseline severity, or patient age. The consistency of the response over time was also evaluated. METHODS: A multicenter, randomized, double-blind, placebo-controlled at-home study of vardenafil treatment (5, 10, and 20 mg) was performed. This secondary analysis compared the mean International Index of Erectile Function (IIEF) erectile function domain scores of various subgroups at 12 weeks of treatment. These populations included organic, psychogenic, or mixed etiologies; mild, moderate, or severe baseline severity; and four age groups (younger than 45, 45 to 55, 56 to 65, and older than 65 years). In addition, all IIEF domains were compared at sequential 4-week periods, before and during treatment. RESULTS: In the 580 men of the intent-to-treat population, the mean erectile function domain scores were statistically greater than placebo, irrespective of etiology, baseline severity, or age. This was seen at all dosages. Compared with placebo, vardenafil statistically improved the IIEF domain scores of erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction after 4 weeks of treatment, and these improvements were maintained for 12 weeks. The rates of the most common adverse events (headache, flushing, and dyspepsia) were either constant or declined over time; they were generally mild to moderate and transient in nature. CONCLUSIONS: Vardenafil improved erectile function regardless of the general etiology, baseline severity of erectile dysfunction, or patient age. Improvements in erectile function and other key IIEF domains were consistently seen throughout the study. Journal ISSN: 1527-9995 Issue: 62-3 (2003) Pages: 519-23; discussion 523-4
Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules.
Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles. Journal ISSN: 1476-4687 Issue: 425-6953 (2003) Pages: 98-102
Induction of suppression by a murine nonspecific suppressor-inducer cell line (M1-A5). II. The role of prostaglandins.
Induction of suppression by a murine nonspecific suppressor-inducer cell line (M1-A5). II. The role of prostaglandins. A murine nonspecific suppressor-inducer cell line (M1-A5) was generated from the spleen cells of a mouse bearing an advanced methylcholanthrene-induced fibrosarcoma. We previously demonstrated the capability of M1-A5 cells to activate suppressor cells from the spleen cells of unprimed mice. We demonstrate here that induction of suppression by M1-A5 cells was blocked by acetylsalicylic acid (ASA) and ibuprofen at concentrations which block prostaglandin (PG) synthesis. Maximal blockade of the induction of suppression by M1-A5 cells was seen when ASA was added at the initiation of culture, and it required inhibition of PG synthesis at the level of the inducer (M1-A5 cells) population. However, ASA blockade of suppressor cell activation by M1-A5 cells was not due to ASA acetylating suppressor-inducing factor. Exogenously added PGE1, PGE2, and PGI2, but not PGF2 alpha or PGD2, were able to restore the inducing capability of M1-A5 cells, which had been blocked by ASA. However, PGE1, PGE2, or PGI2 did not reconstitute an inactive suppressor-inducing factor. These results suggest that PG act to modulate the release of suppressor-inducing factor from M1-A5 cells. Journal ISSN: 0022-1767 Issue: 136-6 (1986) Pages: 1982-7
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