vardenafil, Levitra
Simultaneous administration of vardenafil and tamsulosin does not induce clinically significant hypotension in patients with benign prostatic hyperplasia.

Auerbach SM, Gittelman M, Mazzu A, Cihon F, Sundaresan P, White WB.

California Professional Research, Newport Beach, California 92660, USA.

OBJECTIVES: To assess the pharmacodynamic effects of coadministered vardenafil and tamsulosin in patients with benign prostatic hyperplasia (BPH) undergoing stable tamsulosin therapy. METHODS: In this Phase 1, placebo-controlled, two-stage, two-way, crossover study, 22 patients undergoing stable (longer than 4 weeks) tamsulosin therapy for BPH (18 using 0.4 mg and 4 using 0.8 mg tamsulosin daily) received vardenafil 10 mg (or placebo), followed by vardenafil 20 mg (or placebo), simultaneously with tamsulosin. The mean maximal change from baseline with vardenafil use versus placebo was evaluated for supine and standing blood pressure and heart rate for up to 6 hours after dosing. RESULTS: In patients receiving vardenafil 10 mg, the mean maximal change from baseline versus placebo in supine systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate was -4.5 mm Hg (95% confidence interval [CI] -8.2 to -0.8), -2.3 mm Hg (95% CI -4.9 to 0.4), and 3.7 beats per minute (95% CI 1.1 to 6.3), respectively. In patients receiving vardenafil 20 mg, the mean maximal change from baseline versus placebo in supine SBP, DBP, and heart rate was -4.0 mm Hg (95% CI -6.3 to -1.8), -2.9 mm Hg (95% CI -5.6 to -0.2), and 0.8 beats per minute (95% CI -1.2 to 2.9), respectively. These hemodynamic changes were similar to those obtained in the standing position. Two placebo patients and 1 vardenafil 10-mg patient had a drop of 20 mm Hg or more in standing DBP; 1 vardenafil 10-mg patient had a standing SBP drop of 30 mm Hg or more. No patient exhibited symptomatic hypotension (SBP less than 85 mm Hg with dizziness). Three patients receiving vardenafil 20 mg/tamsulosin 0.4 mg reported dizziness, but never had an SBP of less than 95 mm Hg. No serious adverse events were reported. CONCLUSIONS: In this study, no evidence was found that coadministered vardenafil and tamsulosin induced clinically significant hypotension in patients with BPH.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15533493&dopt=Abstract vardenafil Levitra



vardenafil, Levitra
High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients.

Weeks JL, Zoraghi R, Beasley A, Sekhar KR, Francis SH, Corbin JD.

1Department of Molecular Physiology and Biophysics, Vanderbilt University, School of Medicine, Nashville, Tennessee, USA.

The physiological role of phosphodiesterase (PDE)11 is unknown and its biochemical characteristics are poorly understood. We have expressed human His-tagged PDE11A4 and purified the enzyme to apparent homogeneity. PDE11A4 displays K(m) values of 0.97 muM for cGMP and 2.4 muM for cAMP, and maximal velocities were 4- to 10-fold higher for cAMP than for cGMP. Given the homology between PDE11 and PDE5, we have compared the biochemical potencies of tadalafil (Cialistrade mark, Lilly-ICOS), vardenafil (Levitratrade mark, Bayer-GSK), and sildenafil (Viagratrade mark, Pfizer Inc.) for PDE11A4 and PDE5A1. PDE5A1/PDE11A4 selectivities are 40-, 9300-, and 1000-fold for tadalafil, vardenafil, and sildenafil, respectively. This suggests that none of these three compounds is likely to crossreact with PDE11A4 in patients.International Journal of Impotence Research (2005) 17, 5-9. doi:10.1038/sj.ijir.3901283 Published online 11 November 2004.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15538396&dopt=Abstract vardenafil Levitra



vardenafil, Levitra
The phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil.

Saenz de Tejada I, Angulo J, Cuevas P, Fernandez A, Moncada I, Allona A, Lledo E, Korschen HG, Niewohner U, Haning H, Pages E, Bischoff E.

Fundacion para la Investigacion y el Desarrollo en Andrologia, Madrid, Spain. isaenz ntserver.coronadoserv.com

We investigated the potency and the selectivity profile of vardenafil on phosphodiesterase (PDEs) enzymes, its ability to modify cGMP metabolism and cause relaxation of penile smooth muscle and its effect on erections in vivo under conditions of exogenous nitric oxide (NO) stimulation. PDE isozymes were extracted and purified from human platelets (PDE5) or bovine sources (PDEs 1, 2, 3, 4 and 6). The inhibition of these PDEs and of human recombinant PDEs by vardenafil was determined. The ability to potentiate NO-mediated relaxation and influence cGMP levels in human corpus cavernosum strips was measured in vitro, and erection-inducing activity was demonstrated in conscious rabbits after oral administration together with intravenous doses of sodium nitroprusside (SNP). The effects of vardenafil were compared with those of the well-recognized PDE5 inhibitor, sildenafil (values for sildenafil in brackets). Vardenafil specifically inhibited the hydrolysis of cGMP by PDE5 with an IC50 of 0.7 nM (6.6 nM). In contrast, the IC50 of vardenafil for PDE1 was 180 nM; for PDE6, 11 nM; for PDE2, PDE3 and PDE4, more than 1000 nM. Relative to PDE5, the ratios of the IC50 for PDE1 were 257 (60), for PDE6 16 (7.4). Vardenafil significantly enhanced the SNP-induced relaxation of human trabecular smooth muscle at 3 nM (10 nM). Vardenafil also significantly potentiated both ACh-induced and transmural electrical stimulation-induced relaxation of trabecular smooth muscle. The minimum concentration of vardenafil that significantly potentiated SNP-induced cGMP accumulation was 3 nM (30 nM). In vivo studies in rabbits showed that orally administered vardenafil dose-dependently potentiated erectile responses to intravenously administered SNP. The minimal effective dose that significantly potentiated erection was 0.1 mg/kg (1 mg/kg). The selectivity for PDE5, the potentiation of NO-induced relaxation and cGMP accumulation in human trabecular smooth muscle and the ability to enhance NO-induced erection in vivo indicate that vardenafil has the appropriate properties to be a potential compound for the treatment of erectile dysfunction. Vardenafil was more potent and selective than sildenafil on its inhibitory activity on PDE5.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11890515&dopt=Abstract vardenafil Levitra



vardenafil, Levitra
[Cardiovascular safety of vardenafil]

[Article in Chinese]

Xin Z.

Department of Urology, Peking University First Hospital, Beijing 100034, China.

Vardenafil is a new type of PDE5 inhibitor (PDE5I) with great inhibiting potential on PDE5 (IC50: 0.01 nmol/L) for enhancing erectile function. International and domestic clinical studies showed it to be safe and effective in treating ED with mild temporary side effects such as headache, dizziness, flushing and rhinitis. In this paper we reviewed the cardiovascular safety of vardenafil. Studies showed that clinical dosage of vardenafil could decrease the systematic arterial blood pressure mildly (< 10 mmHg) , however, it did not interact in a potentially hazardous way with antihypertensive or antianginal therapy, with the exception of organic nitrates. Vardenafil slightly prolonged the QT interval (QTc) in cardiac repolarization, but with no evidence to prove that it could cause arrhythmia in clinical studies. The rates and categories of cardiovascular adverse events of vardenafil therapy were not significantly different from placebo in 5 clinical trials. Present studies demonstrated that clinical dosage of vardenafil appeared generally well tolerated in most patients with chronic and stable cardiovascular disease and it was an ideal drug for the first line treatment of ED.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15562797&dopt=Abstract vardenafil Levitra



vardenafil, Levitra
[Vardenafil for the treatment of erectile dysfunction in men with diabetes]

[Article in Chinese]

Wang X.

Department of Urology, Chinese PLA General Hospital, Beijing 100853, China.

The prevalence of erectile dysfunction (ED) is higher in diabete patients than in non-diabete men. Moreover, the treatment of ED is more challenging in men with diabetes. Vardenafil, a novel and highly selective phosphodiesterase 5 inhibitor, is the first line therapy for the broad ED population. Recent large-scale clinical trials indicated that vardenafil improved erectile function in ED men with diabetes regardless of the baseline ED severity and plasma HbA1c levels, and it was generally well tolerated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15562798&dopt=Abstract vardenafil Levitra