Evaluation of the effects of Sildenafil Citrate (Viagra) on canine renal artery, carotid and aortic blood flow with the aid of color Doppler sonography.

INTRODUCTION: Erectile Dysfunction is the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. Oral use of Sildenafil Citrate (Viagra) has been proved to be effective in the treatment of Erectile Dysfunction. Although the effects of Sildenafil Citrate (Viagra) have been investigated in several studies, its effect on aortic, carotid and renal artery blood flow is unknown. The aim of this study was to investigate the early and late phase effects of Sildenafil Citrate (Viagra) on canine aortic, carotid and renal artery blood flow using color Doppler sonography (CDS). MATERIALS AND METHODS: A total of 6 healthy adult dogs was used in this study. With the aid of CDS peak systolic flow rate, end diastolic flow rate, resistivity index (RI) and pulsatility index in aortic, renal and carotid artery were determined before the administration of Sildenafil Citrate (Viagra), 45-75 min after drug administration and after 15 days of drug administration. Data were statistically analyzed using Friedman and Wilcoxon rank tests. p < 0.05 was considered to be statistically significant. RESULTS AND CONCLUSIONS: Significant changes were determined in only 4 out of 28 parameters studied. The significantly changed parameters were as follows: a significant increase in the early and late phase of the postdrug peak of systolic aortic blood flow compared to values before drug administration, an increase in pre- and postdrug RI values of the aorta, a significant decrease in maximum velocity of the right carotid artery, and peak systolic maximum velocity of the left renal segmental artery after drug administration compared to their respective predrug basal values. The results from this study indicate that Sildenafil Citrate (Viagra) has no significant effects on aortic, renal and carotid artery blood flow rate either in the early or in the late phase. Since this study involved only 6 dogs there is a need for further clinical studies involving larger groups of subjects to conclude that this drug is safe with respect to the hemodynamic parameters evaluated in this study.

Efficacy and safety of Sildenafil Citrate (Viagra) in the treatment of Erectile Dysfunction in patients with ischemic heart disease.

Erectile Dysfunction is a common condition in men with cardiovascular disease, probably as a result of shared factors that impair hemodynamic mechanisms in the penile and ischemic vasculature. Sildenafil Citrate (Viagra), an orally active, selective inhibitor of phosphodiesterase type 5 (PDE5), has demonstrated excellent efficacy and safety profiles in men with Erectile Dysfunction of various etiologies.Sildenafil Citrate (Viagra) administration is contraindicated in patients who are taking nitrates or nitric oxide donors. This retrospective subanalysis of data from double-blind, placebo-controlled studies assessed the efficacy (9 studies) and safety (11 studies) ofSildenafil Citrate (Viagra) in patients with Erectile Dysfunction and ischemic heart disease who were not taking nitrates. Of 3,672 patients randomized to receiveSildenafil Citrate (Viagra) (5-200 mg) or placebo for 4-24 weeks in 11 double-blind, placebo-controlled studies, 357 (10%) reported a history (past or present) of ischemic heart disease and were not taking nitrates. Efficacy was assessed using end-of-treatment responses to Question 3 (ability to achieve an erection) and Question 4 (ability to maintain an erection) of the International Index of Erectile Function (IIEF), scores for the 5 domains of male sexual function assessed by the IIEF (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), and responses to a global efficacy question ("Did the treatment improve your erections?"). The responses to the 2 IIEF questions were graded on a scale of 1 (almost never or never) to 5 (almost always or always), with a score of 0 indicating no attempt at sexual intercourse. At the end of treatment, the mean scores for Question 3 and Question 4 of the IIEF for patients with Erectile Dysfunction and ischemic heart disease were significantly higher for theSildenafil Citrate (Viagra) group than for the placebo group (p <0.0001). Mean end-of-treatment scores for the IIEF domains also demonstrated significant increases for sildenafil-treated patients compared with those receiving placebo (p <0.05). At the end of treatment, improved erections were reported by 70% of patients who receivedSildenafil Citrate (Viagra) and by 20% of those in the placebo group p <0.0001). For theSildenafil Citrate (Viagra) group, the incidences of the most common adverse events (headache 25%, flushing 14%, and dyspepsia 12%) for patients with ischemic heart disease were similar to those in patients without this concomitant illness (21%, 15%, and 10%, respectively). Moreover, the overall incidence of cardiovascular adverse events other than flushing was comparable in patients with and without ischemic heart disease for both treatment groups. Since there is a degree of cardiac risk associated with sexual activity, clinicians should consider the patient's cardiovascular status before initiating any treatment for Erectile Dysfunction. Physicians should be aware that patients with underlying cardiovascular disease could be adversely affected by the vasodilator effects of sildenafil, especially in combination with sexual activity. The results of the present subanalysis indicate that oralSildenafil Citrate (Viagra) significantly improves erectile function and is well tolerated in patients with Erectile Dysfunction and ischemic heart disease who are not taking nitrate therapy

Sildenafil selectively inhibits acute pulmonary embolism-induced pulmonary hypertension.

Selective pulmonary vasodilators attenuate acute pulmonary embolism (APE)-induced pulmonary hypertension. We examined the effects of intravenousSildenafil Citrate (Viagra) on the hemodynamic and respiratory changes caused by APE in anesthetized dogs. Sham operated animals (n=3) received only saline infusions. APE was induced by intravenous injections of microspheres in amounts adjusted to increase mean pulmonary artery pressures (MPAP) by 20mmHg. Hemodynamic evaluation was performed and arterial blood samples were drawn for blood gas analysis at baseline, 15 and 30min after APE was induced, and then 15, 30, and 45min after theSildenafil Citrate (Viagra) infusion (1mgkg(-1) infused intravenously in 15min followed by 0.3mgkg(-1)h(-1) for 30min) started in theSildenafil Citrate (Viagra) group (n=7), or saline infusion started in the control group (n=8). APE induced sustained pulmonary hypertension and 325% increase in pulmonary vascular resistance index (PVRI) without significant changes in the other hemodynamic parameters. While the animals in the control group showed no further changes in MPAP and PVRI, a significant decrease in MPAP and PVRI (-25 and -45%, respectively; P<0.05 both) was observed with sildenafil. No significant changes in the other hemodymamic parameters were observed in both groups. APE decreased PaO(2), whereasSildenafil Citrate (Viagra) attenuated the decrease in PaO(2) (P<0.05). We conclude that intravenousSildenafil Citrate (Viagra) can selectively attenuate the increases in MPAP and PVRI after APE

Determination of Sildenafil Citrate (Viagra) and related substances in the commercial products and tablet dosage form using HPLC.

This study aimed at developing and validating an HPLC method for the assay of Sildenafil Citrate (Viagra) and its related substances that might coexist in the drug commercial products and in tablets' formulation as impurities that originate from synthesis processes or degradation. A chromatographic system comprising a microBondapak C(18) (10 microm) column, a mobile phase of ammonium acetate (pH 7.0, 0.2 M)-acetonitrile (1:1, v/v), a flow rate of 1 ml/min and a UV detector set at 240 nm has shown good chromatographic separation for sildenfil and the other related substances. The degree of linearity of the calibration curves, the percent recoveries ofSildenafil Citrate (Viagra) and related substances, the limit of detection, LOD, and limit of quantitation, LOQ for the HPLC method have been determined. The HPLC method under study was found to be specific, precise, accurate, reproducible indicating stability and robust

Sildenafil Citrate (Viagra) corrects DeltaF508-CFTR location in nasal epithelial cells from patients with cystic fibrosis.

BACKGROUND: Most patients with cystic fibrosis (CF) have a DeltaF508 mutation resulting in abnormal retention of mutant gene protein (DeltaF508-CFTR) within the cell. This study was undertaken to investigate DeltaF508-CFTR trafficking in native cells from patients with CF with the aim of discovering pharmacological agents that can move DeltaF508-CFTR to its correct location in the apical cell membrane. METHOD: Nasal epithelial cells were obtained by brushing from individuals with CF. CFTR location was determined using immunofluorescence and confocal imaging in untreated cells and cells treated with sildenafil. The effect ofSildenafil Citrate (Viagra) treatment on CFTR chloride transport function was measured in CF15 cells using an iodide efflux assay. RESULTS: In most untreated CF cells DeltaF508-CFTR was mislocalised within the cell at a site close to the nucleus. Exposure of cells toSildenafil Citrate (Viagra) (2 hours at 37 degrees C) resulted in recruitment of DeltaF508-CFTR to the apical membrane and the appearance of chloride transport activity.Sildenafil Citrate (Viagra) also increased DeltaF508-CFTR trafficking in cells from individuals with CF with a single copy DeltaF508 (DeltaF508/4016ins) or with a newly described CF trafficking mutation (R1283M). CONCLUSIONS: The findings provide proof of principle forSildenafil Citrate (Viagra) as a DeltaF508-CFTR trafficking drug and give encouragement for future testing ofSildenafil Citrate (Viagra) and related PDE5 inhibitors in patients with CF

Determination of a new phosphodiesterase V inhibitor, DA-8159, in plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method using liquid-liquid extraction for sample preparation was developed for the determination of a new phosphodiesterase V inhibitor, DA-8159, in rat plasma and urine using Sildenafil Citrate (Viagra) as an internal standard. A 100 microl aliquot of 0.1 M Na(2)CO(3) (containing Sildenafil Citrate (Viagra), 3 microg/ml as free sildenafil) and a 1 ml aliquot of ether were added to a 100 microl aliquot of biological samples (urine samples were diluted 20 times with distilled water). After vortex centrifugation at 9000 x g for 3 min, the ether layer was collected and dried under nitrogen gas. The residue was reconstituted with a 150 microl aliquot of the mobile phase, centrifuged, and a 100 microl aliquot of the supernatant was injected onto a reversed-phase column. The mobile phases, 20 mM KH(2)PO(4) (pH 4.7):acetonitrile (70:30, v/v for plasma and tissue samples, and 75:25, v/v for urine samples), were run at a flow rate of 1.0 ml/min. The column effluent was monitored by an ultraviolet detector set at 292 nm. The retention times for DA-8159 and the internal standard were approximately 10.7 and 9.1 min, respectively, in plasma and tissue samples and the corresponding values in urine samples were 47 and 33 min. The detection limits for DA-8159 in rat plasma and urine were 20 and 100 ng/ml, respectively. The coefficients of variation of the assay were generally low: below 10% for plasma and 9.9% for urine. No interferences from endogenous substances were found.

Quality control in the urologist's practice Erectile Dysfunction as an example of a multi-centered approach to documenting treatment results in urologist practices.

Of 517 urologist practices approached, 93% participated in a pilot study on the quality of care in the treatment of Erectile Dysfunction (ED). Treatment modalities and satisfaction were documented for 10,750 ED patients in 2002-at a time when vardenafil and tadalafil had not yet been officially approved. Psychological factors (55%), BPH (42%), and hypertension (33%) were given as the most prevalent ED risk factors; 82% of the patients received sildenafil, 20% apomorphine, 12% yohimbine, and 10% intracavernous alprostadil. Of the patients, 81% were satisfied or very satisfied with one of the treatment options offered and 85% and more were satisfied or very satisfied with sildenafil's onset of action, duration of action, efficacy, and tolerability. Of the physicians, 97% rated the opportunity to compare their own treatment results with other urologists' results as important or very important

Potentiation of sildenafil-induced hypotension is minimal with nitrates generating a radical intermediate.

Recently the new specific phosphodiesterase-5 inhibitorSildenafil Citrate (Viagra) was introduced into therapy for Erectile Dysfunction. Because of the phosphodiesterase-5 inhibitor-induced increases of cyclic GMP in the vasculature, vasodilation in various vascular beds is induced, which in combination with various nitrovasodilators (e.g., when used simultaneously for the treatment of coronary artery disease), may lead to excessive hypotension. Thus nitrovasodilators are contraindicated whenSildenafil Citrate (Viagra) may be used and reports of a number of accidents have recently been published. We therefore studied the acute interactions of glyceryl trinitrate (GTN), pentaerythritol tetranitrate (PETN), and isosorbide dinitrate (ISDN) withSildenafil Citrate (Viagra) in six chronically instrumented conscious dogs for each nitrate to assess the magnitude of blood pressure drops (and compensatory increases in heart rate) during a 24-h nitrate administration (infusion into the pulmonary artery).Sildenafil Citrate (Viagra) (3 mg/kg) was given orally (after a 24-h fast) 30 min after start of nitrate infusion. GTN, PETN, or ISDN (which follow different steps of metabolic conversion to nitric oxide) were applied at submaximal dosages leading to 90% of maximal coronary artery dilation at 1.5 microg/kg per min, 0.75 microg/kg per min, or 6 microg/kg per min, respectively. During GTN infusionSildenafil Citrate (Viagra) caused a maximum drop in mean blood pressure of 21 +/- 3 mm Hg (rise in heart rate from 117.0 +/- 7.2 to 126.0 +/- 6 .0/min) and during ISDN infusion of 18 +/- 3 mm Hg (rise in heart rate from 115.0 +/- 7.0 to 125 +/- 6/min), which was significantly less (p < 0.01) during PETN (only 6 +/- 1 mm Hg with a rise in heart rate from 107.0 +/- 5.0 to 122.0 +/- 7.0/min). WhenSildenafil Citrate (Viagra) is used during exposure to nitrates (e.g., in coronary artery disease), the PETN-induced drop in blood pressure at equi-effective dosages (with regard to coronary dilation) is substantially smaller compared with that of GTN or ISDN, which is probably because of lesser potentiation of phosphodiesterase-5 inhibitor-induced effects in the arteriolar bed, thus minimizing critical drops in blood pressure