vardenafil, Levitra
Absence of clinically important HERG channel blockade by three compounds that inhibit phosphodiesterase 5--sildenafil, tadalafil, and vardenafil.

Dustan Sarazan R, Crumb WJ Jr, Beasley CM Jr, Emmick JT, Ferguson KM, Strnat CA, Sausen PJ.

Lilly Research Laboratories, Eli Lilly and Company, 2001 W. Main St., Greenfield, Indianapolis, IN 46140, USA. sarazan lilly.com

Compounds that inhibit phosphodiesterase 5 (PDE5) have been developed for the treatment of erectile dysfunction. Because men with erectile dysfunction frequently have comorbid cardiovascular disease, they may have limited cardiac repolarization reserve and be at risk of arrhythmia if treated with medications that prolong ventricular repolarization. The human ether-a-go-go related gene (HERG) channel is important for repolarization in human myocardium and is a common target for drugs that prolong the QT interval. We studied the ability of three compounds that inhibit PDE5--sildenafil, tadalafil, and vardenafil--to block the HERG channel. Using a whole cell variant of the patch-clamp method, the HERG current was measured in a stably transfected human embryonic kidney cell line expressing the HERG channel. The compounds produced dose-dependent reductions in HERG current amplitude over a concentration range of 0.1 to 100 microM. The IC50 values were 12.8 microM for vardenafil and 33.3 microM for sildenafil. Because the maximum soluble concentration of tadalafil (100 microM) produced only a 50.9% inhibition of the HERG current amplitude, the IC50 value for tadalafil could not be determined with the Hill equation. Tadalafil had the weakest capacity to block the HERG channel, producing a 50.9% blockade at the maximum soluble concentration (100 microM), compared with 86.2% for vardenafil (100 microM) and 75.2% for sildenafil (100 microM). In conclusion, the concentrations of the PDE5 inhibitors required to evoke a 50% inhibition of the HERG current were well above reported therapeutic plasma concentrations of free and total compound. None of the three compounds was a potent blocker of the HERG channel.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15476742&dopt=Abstract vardenafil Levitra



vardenafil, Levitra
[Efficacy and safety of vardenafil for men with erectile dysfunction]

[Article in Chinese]

Zhu J, Jiang H.

Department of Urology, the Peoples Hospital of Peking University, Beijing 100044, China.

Vardenafil is an oral, potent, highly selective phosphodiesterase 5 (PDE5) inhibitor. It improves erectile function significantly regardless of the etiology and severity of erectile dysfunction (ED) or the age of the patients. Its onset time leading to successful intercourse is as short as 10 minutes after administered orally, and in most patients it works persistently. Adverse reactions are generally transient and mild to moderate in nature. So vardenafil is both effective and safe for men with ED.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15497716&dopt=Abstract vardenafil Levitra



vardenafil, Levitra
[Pharmacodynamics and pharmacokinetics of vardenafil in patients with erectile dysfunction]

[Article in Chinese]

Jin J, Guo Y.

Peking University First Hospital, Institute of Urology, Beijing 100034, China. jinjie vip.163.com

Vardenafil is a potent and highly selective phosphodiesterase type 5 (PDE5) inhibitor with a potency about 10-fold higher than sildenafil. Vardenafil can significantly improve erectile function and works rapidly. Vardenafil is a PDE5 inhibitor with the fastest onset of action among its kind so far found and works as early as 10 minutes after oral administration, providing patients with penile erection sufficient to complete an intercourse. The absolute oral bioavailability is about 15%. Vardenafil is rapidly absorbed with a median tmax of 0.7 h and a terminal half-life (t1/2) of more than 4 h. The observed pharmacodynamic properties, pharmacokinetic characteristics and good safety and tolerability profile showed that vardenafil treatment provides an effective and generally well tolerated treatment for ED.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15497717&dopt=Abstract vardenafil Levitra



vardenafil, Levitra
Analysis of undeclared synthetic phosphodiesterase-5 inhibitors in dietary supplements and herbal matrices by LC-ESI-MS and LC-UV.

Gratz SR, Flurer CL, Wolnik KA.

US Food and Drug Administration, Forensic Chemistry Center, Cincinnati, OH 45237-3097, USA. sgratz ora.fda.gov

A liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) method was developed to screen for the presence of synthetic phosphodiesterase type 5 (PDE-5) inhibitors including sildenafil, tadalafil and vardenafil. The method was applied to the analysis of dietary supplements and bulk herbal materials. Bulk powders or composites of tablets, capsules or liquids were prepared and an extraction of PDE-5 inhibitors was performed using a mixture of acetonitrile and water with sonication. Identification of sildenafil, vardenafil or tadalafil was accomplished using a single quadrupole mass spectrometer coupled to a liquid chromatograph with an electrospray interface. Positive ion detection in the full scan mode was used while in-source collision induced dissociation (CID) provided several structurally significant fragment ions to aid in the mass spectral identification. Approximately half of the 40 botanical products analyzed were found to contain undeclared synthetic PDE-5 inhibitors. For products found to contain one of these three compounds by LC-MS, HPLC with UV detection was used for quantitation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15522526&dopt=Abstract vardenafil Levitra



vardenafil, Levitra
Development of a Micellar electrokinetic capillary chromatography method for the determination of three drugs employed in the erectile dysfunction therapy.

Rodriguez Flores J, Berzas Nevado JJ, Castaneda Penalvo G, Mora Diez N.

Department of Analytical Chemistry and Foods Technology, UCLM 13071, Ciudad Real, Spain. juana.rflores uclm.es

A Micellar electrokinetic capillary chromatography method is proposed for the determination of sildenafil, vardenafil and tadalafil, which are employed in oral therapy for erectile dysfunction. Optimum conditions for the separation were investigated. A background electrolyte solution consisting of 10 mM phosphate buffer adjusted to pH 12.0, sodium dodecyl sulfate (SDS) 25 mM, hydrodynamic injection, and 25 kV as separation voltage were used. Relative standard deviations (R.S.D.s) were 1.0, 1.0, 0.4% and 2.9, 2.9, 1.9% for migration time and corrected peak area (CPA) (n = 9) for sildenafil, vardenafil and tadalafil, respectively. Detection limits obtained for the three drugs ranged from 0.19 to 0.61 mg L(-1). A linear concentration range between 1 and 20 mg L(-1) was obtained. A ruggedness test of this method was checked using the fractional factorial model of Plackett-Burman, in which the influence of six factors at three different levels was tested on different electrophoretic results: resolution and corrected peak area. The statistical evaluation of the electrophoretic results was achieved by Youden and Steiner method. The described method is rapid, sensitive and rugged and it was tested in the pharmaceutical formulations analysis obtaining recoveries between 98 and 107% respect to the nominal content.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15522725&dopt=Abstract vardenafil Levitra