Gene/Protein Disease Symptom Drug Enzyme Compound
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 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IC351 (Cialis) is a selective inhibitor of PDE5. The efficacy and safety of on-demand dosing of IC351 in men with erectile dysfunction was assessed in a multicenter, double-blind, placebo-controlled study. One hundred seventy-nine men (mean age: 56 y) were randomized to receive placebo or IC351 at doses of 2, 5, 10 or 25 mg, taken on demand over a 3-week period. The primary endpoints were change from baseline in responses to Questions 3 (Q3) and 4 (Q4) of the International Index of Erectile Function (IIEF). IC351 significantly improved IIEF Q3 scores at all doses vs placebo (P < or =0.003). IC351 also significantly improved IIEF Q4 scores in all but the 2 mg group (P < or =0.0003). No significant changes in laboratory values, ECGs, or blood pressure were observed. The most common adverse events were headache and dyspepsia. The conclusion of this study was that on-demand IC351 at doses up to 25 mg was well tolerated and significantly improved erectile function.
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PMID:On-demand IC351 (Cialis) enhances erectile function in patients with erectile dysfunction. 1131 31

Sildenafil is an oral treatment for erectile dysfunction (ED). It acts as an inhibitor of 3',5'-cyclic guanosine monophosphate-phosphodiesterase type 5. An effective treatment for ED is required to produce an erectile response sufficient for satisfactory sexual performance. This has been documented for sildenafil in men with ED of differing aetiologies and baseline severity in various types of clinical trials. Sildenafil treatment is characterised by a good tolerability profile and low treatment digcontinuation rate caused by treatment-related adverse effects. Most of the adverse effects associated with sildenafil are extensions of the pharmacological action of the drug. There is no significant difference in the adverse effect profile (headache, flushing, dyspepsia, nasal congestion and abnormal vision) of this agent as assessed by clinical data obtained either in the pre- and postlaunch periods. Because of its acceptable risk-benefit ratio, sildenafil can be prescribed to a very large group of patients with ED. The reports of serious cardiovascular events associated with the use of sildenafil (including anecdotal reports of deaths) have been very thoroughly analysed. A number of studies have not shown any difference in the risk of serious cardiovascular events in sildenafil- and placebo-treated patients. However, when making a risk-benefit evaluation, certain subgroups of patients need to be considered separately. In particular, sildenafil is contraindicated in patients receiving nitrate therapy. In some other subgroups of patients, the risks and benefits of treatment need to be assessed on an individual basis and it is hoped that additional data will clarify any possible risks associated with sildenafil administration such patients. It is helpful to compare the risk-benefit profile of sildenafil with the characteristics of other oral drugs for ED. According to the preliminary data, apomorphine and phentolamine are possible future options for the treatment of ED; however, there needs to be further clinical evaluation of these agents. Initial data have shown that sildenafil can be successfully combined with intracavernosal injection in patients nonresponders to either therapy. In conclusion, favourable characteristics make sildenafil suitable for the first-line therapy for a substantial proportion of patients with ED.
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PMID:A risk-benefit assessment of sildenafil in the treatment of erectile dysfunction. 1133 Jun 55

Vardenafil, a novel selective phosphodiesterase type 5 inhibitor, was evaluated in its first large-scale at-home trial. A total of 601 men with mild to severe erectile dysfunction (ED) were enrolled in this multi-centre, randomized, double-blind, placebo-controlled trial of 12 weeks of treatment with either placebo or 5, 10 and 20 mg of vardenafil. Primary endpoints were Q3 (vaginal penetration) and Q4 (maintenance of erection) of the International Index of Erectile Function (IIEF). In the intent-to-treat population (n=580), the changes from baseline for 5, 10 and 20 mg vardenafil (1.2, 1.3 and 1.5, respectively) were all improved (P<0.001) over placebo (0.2) for Q3 and were similarly improved for Q4 (1.4, 1.5 and 1.7) compared to placebo (0.5) (P<0.001). All vardenafil doses improved all IIEF domains compared to placebo (P<0.001). The percentage of successful intercourses was between 71 and 75% for the three vardenafil doses. For the 20 mg dose, 80% of the patients experienced improved erections (GAQ) compared to 30% for placebo. Most frequent treatment-emergent adverse events were headache (7-15%), flushing (10-11%) and up to 7% for dyspepsia or rhinitis. Vardenafil treatment resulted in a high efficacy and low adverse-event profile in a population with mixed ED etiologies.
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PMID:The efficacy and tolerability of vardenafil, a new, oral, selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction: the first at-home clinical trial. 1149 74

The efficacy and safety of sildenafil were evaluated in a randomised, double-blind, placebo-controlled, flexible-dose study in Taiwanese men aged 26 to 80 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months' duration. A total of 236 patients were randomised at six medical centres in Taiwan to receive either sildenafil (50 mg initially increased if necessary to 100 mg or decreased to 25 mg depending on efficacy and toleration) (n=119) or matching placebo (n=117) taken on an 'as needed' basis 1 h prior to anticipated sexual activity for a period of 12 weeks. At the end of 12 weeks, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the IIEF (International Index of Erectile Function) scale, (2) the percentage of successful intercourse attempts; and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P<0.0001). Treatment-related adverse events occurred in 43.7% of patients receiving sildenafil and 18.8% receiving placebo. The most common adverse events with sildenafil were flushing, dizziness and headache (25.2, 6.7 and 5.9% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in the population of Taiwanese men appears similar to that reported in other studies in western populations.
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PMID:ASSESS-3: a randomised, double-blind, flexible-dose clinical trial of the efficacy and safety of oral sildenafil in the treatment of men with erectile dysfunction in Taiwan. 1149 79

Sublingual (SL) apomorphine (2 to 6 mg) has been shown to be effective for treatment of male erectile dysfunction. Many patients with erectile dysfunction are also being treated for systemic hypertension and/or cardiovascular disease. In a double-blind, randomized, placebo-controlled, crossover trial, SL apomorphine 5 mg and placebo were administered on alternate days to 162 men who were on long-term therapy (> or =4 weeks) with angiotensin-converting enzyme inhibitors, beta blockers, diuretics, calcium channel blockers, alpha(1) blockers, or short- or long-acting nitrates. Blood pressure and heart rate were measured before and after dosing; cardiac rhythm was recorded by 4-hour Holter monitoring. The only potentially clinically significant interactions between SL apomorphine and the antihypertensive agents or short-acting nitrates were greater orthostatic decreases in systolic blood pressure in the alpha-blocker and calcium channel blocker groups (-10 and -6 mm Hg vs placebo, respectively). Administration of SL apomorphine after dosing with long-acting nitrates resulted in significant decreases in blood pressure when patients were standing (mean systolic change, -5 to -9 mm Hg 30 to 60 minutes postdose, p <0.05; mean diastolic change, -3 to -4 mm Hg 50 to 60 minutes postdose, p <0.05). The most common adverse events with SL apomorphine were dizziness, nausea, and headache. Syncope occurred in 1 patient in the beta-blocker group; symptomatic hypotension occurred in 2 patients each in the short- and long-acting nitrate groups. Thus, in patients receiving common antihypertensive agents and short-acting nitrates, as well as in most patients receiving long-acting nitrates, SL apomorphine at higher than recommended doses produced no clinically significant changes in heart rate or blood pressure greater than changes seen with SL apomorphine alone.
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PMID:Cardiovascular safety of sublingual apomorphine in patients on stable doses of oral antihypertensive agents and nitrates. 1158 43

Hypertension is an important risk factor for erectile dysfunction (ED). Consequently, there is a high coincidence between hypertension and ED. Oral sildenafil (Viagra) is an effective treatment for ED in patients with treated or untreated hypertension. The most common adverse events of sildenafil (headache, flushing, hypotension) result from its moderate vasodilating properties. The concomitant use of sildenafil and organic nitrates is contraindicated because it may lead to a potentiation of the decreases in blood pressure and thus cause life-threatening hypotension. In contrast, the concomitant use of sildenafil and different classes of antihypertensive agents (beta-blockers, alpha-blockers, diuretics, ACE inhibitors, calcium antagonists) may lead to additive but not to potentiating blood pressure decreases. Thus, this combination is unlikely to cause clinically significant hypotension or an increased incidence of adverse events. Sildenafil is an effective and well-tolerated treatment for ED in patients taking concomitant antihypertensive medication, including those on multidrug regimens.
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PMID:[Interaction between sildenafil and antihypertensive drugs: what is evidence-based?]. 1159 59

IC351 (tadalafil, trade name Cialis) is a new representative compound of the second generation of selective phosphodiesterase 5 (PDE-5) inhibitors. The selectivity ratio vs PDE-5 is more than 10 000 for PDE-1 through PDE-4 and PDE-7 through PDE-10 and 780 for PDE-6. In the European daily-dosing trial, the efficacy rates were up to 93% for successful intercourses with completion in the 50-mg dose in patients with mild to moderate erectile dysfunction (ED). In two different dose-ranging studies with 2-25 mg taken as needed, efficacy rates of up to 88% improvement in erections and up to 73% successful intercourses with completion were achieved. In a placebo-controlled, fixed-dose (10- and 20-mg) trial in diabetic patients, improved erections of 56% and 64% were reported compared with 25% after placebo. Drug-related adverse effects, with headache in up to 23% of patients (placebo, up to 17%), dyspepsia in up to 11% (placebo, up to 7%), back pain in up to 4.7% (placebo, 0%), and myalgia in up to 4.1% (placebo, up to 2.4%), were mostly mild to moderate. Neither drug-related serious cardiovascular adverse events nor color vision disturbances were encountered. The long half-life (>17 h), with a comfortably long window of opportunity, releases couples from the need to plan sexual activities and therefore provides the highest amount of spontaneity for sexual activities.
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PMID:IC351 (tadalafil, Cialis): update on clinical experience. 1185 Jul 37

Long-term efficacy and safety of sildenafil was assessed in 1008 patients with erectile dysfunction (ED) enrolled in four flexible-dose (25 - 100 mg), open-label, 36- or 52-week extension studies. After 36 and 52 weeks, 92% and 89% of patients felt that treatment with sildenafil had improved their erections. Responses to a Sexual Function Questionnaire indicated that 52 weeks of sildenafil treatment resulted in clinically significant improvements in the duration and firmness of erections, overall satisfaction with sex life, and the frequency of stimulated erections. Commonly reported adverse events (AEs) were headache, flushing, dyspepsia, and rhinitis, which were generally mild to moderate. Reports of abnormal vision were consistent with previous clinical trials. The occurrence of treatment-related cardiovascular AEs, such as hypertension, tachycardia, and palpitation, was <1%. Discontinuations due to treatment-related AEs were low (2%). Long-term therapy does not diminish the efficacy of sildenafil in patients with ED and remains well tolerated.
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PMID:Assessment of the efficacy and safety of Viagra (sildenafil citrate) in men with erectile dysfunction during long-term treatment. 1189 May 12

Oral therapy has become first line treatment for patients with mild to moderate erectile dysfunction (ED). Studies have shown that sildenafil may not be effective in all patients, and has been associated with a variety of adverse effects and an adverse interaction with nitrates and inhibitors of cytochrome P450 enzymes. The objective was to compare the efficacy and safety of three different oral combinations with the highest dose of sildenafil in men with moderate to severe ED. Randomized, double blind, unblinded active-controlled, Phase II study was carried out at three sites in Mexico. After a 4-week placebo run-in period, patients received all four of the following treatments using a 4-way cross-over design: 40 mg phentolamine (PM) +6 mg apomorphine (Apo); 40 mg PM +150 mg papaverine (Pap); 40 mg PM +6 mg Apo +150 mg Pap (Tricombo); 100 mg sildenafil (SC). With the exception of sildenafil tablets, all study medication was blinded. Moderate to severe ED was defined as a less than 50% vaginal penetration success rate during the placebo run-in period. A total of 44 patients were enrolled, of whom 36 completed all four treatment periods. All treatments produced a significant effect in primary efficacy variable (Sexual Encounter Profile) compared to baseline, however, no statistically significant differences were found between treatments. A significant period effect was observed. Also, the four treatments were found not to differ significantly in five out of six secondary efficacy variables. The lowest incidence of treatment-related adverse events (AE) occurred in the 40 mg PM +6 mg Apo group (9.8%), followed by 100 mg SC (15%), and the other two combinations (16.7 and 17.5%, respectively). Nasocongestion and headache were the most frequently reported AE. An oral combination of vasoactive agents may provide an alternative approach to sildenafil. Based on these results a combination of phentolamine and apomorphine warrants further clinical investigation.
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PMID:Combination therapy for erectile dysfunction: a randomized, double blind, unblinded active-controlled, cross-over study of the pharmacodynamics and safety of combined oral formulations of apomorphine hydrochloride, phentolamine mesylate and papaverine hydrochloride in men with moderate to severe erectile dysfunction. 1189 79

Safety and tolerability of sildenafil citrate was assessed in a population subset of 60 Singaporean men with erectile dysfunction taken from the Asian Sildenafil Efficacy and Safety Study (ASSESS-I), a double-blind, placebo-controlled, flexible-dose study. The men, from two centres, with > or = 6 months' history of erectile dysfunction, were randomized to two treatment arms for 12 weeks. One group (30 patients) received sildenafil (initial dose 50 mg taken 1 h before sexual activity for the first 2 weeks, increased to 100 mg or decreased to 25 mg, according to efficacy and/or tolerability). The remaining 30 patients received a matching placebo. Incidence and type of adverse effects were evaluated at 2, 4, 8 and 12 weeks. Nine patients (30.0%) on sildenafil (33.1% in the full ASSESS-I study) and one patient (3.3%) on placebo (22.8% in the full ASSESS-I study) experienced treatment-related adverse events, the most frequent being headache in the sildenafil group (reported by five patients [16.7%]; 11.0% in the full ASSESS-I study). Flushing, visual disturbance, dizziness, insomnia, myalgia and back pain each occurred in one patient in the sildenafil group (3.3%); in the placebo group, one patient (3.3%) had headache. Importantly, the incidence of cardiovascular and respiratory system adverse events were relatively less than in the full ASSESS-I population (cardiovascular 3.3% in the present study versus 10.2% in the full ASSESS-I population; respiratory 3.3% versus 5.5%). All adverse events were transient and mild, and did not lead to treatment withdrawal. There was no effect on sitting blood pressure, heart rate or standard laboratory parameters; more importantly, there was no incidence of myocardial infarction, stroke or priapism. These results should reassure Singaporean patients and their physicians of the safety of sildenafil for erectile dysfunction.
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PMID:Clinical safety profile of sildenafil in Singaporean men with erectile dysfunction: pre-marketing experience (ASSESS-I evaluation). 1202 21


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