sildenafil-citrate and avanafil

We carried out a systematic review and meta-analysis to assess the efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors for treating erectile dysfunction (ED) after bilateral nerve-sparing radical prostatectomy (BNSRP). A literature review was performed to identify all published randomised double-blind, placebo-controlled trials of PDE5 inhibitors for the treatment of ED after BNSRP. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Six publications involving a total of 1678 patients were used in the analysis, including six RCTs that compared PDE5 inhibitors (tadalafil, sildenafil, avanafil and vardenafil) with placebo. Co-primary efficacy end points: International Index of Erectile Function-Erectile Function (IIEF-EF) domain score [the standardised mean difference (SMD) = 4.04, 95% confidence interval (CI) = 2.87-5.22, P < 0.00001]; successful vaginal penetration (SEP2) [the odds ratio (OR) = 14.87, 95%CI = 4.57-48.37, P < 0.00001]; and successful intercourse (SEP3) (OR = 47, 95%CI = 3-13.98, P < 0.00001) indicated that PDE5 inhibitors was more effective than the placebo. Specific adverse events with PDE5 inhibitors included headache (12.08%), dyspepsia (6.76%) and flushing (6.52%), which were significantly less likely to occur with placebo. This meta-analysis indicates that PDE5 inhibitors to be an effective and well-tolerated treatment for ED after BNSRP.

Topics: Erectile Dysfunction; Humans; Male; Organ Sparing Treatments; Peripheral Nerves; Phosphodiesterase 5 Inhibitors; Postoperative Complications; Prostatectomy; Pyrimidines; Sildenafil Citrate; Tadalafil; Treatment Outcome; Vardenafil Dihydrochloride

To compare the efficacy and safety of avanafil as compared with sildenafil in the management of patients with erectile dysfunction.. It was a prospective, randomized, double-blind, two-arm, active-controlled, parallel, multicenter, non-inferiority clinical study carried out in patients with erectile dysfunction for at least 3 months and International Index of Erectile Function - Erectile Function domain score of <26 at enrolment.. A total of 220 patients were randomized to receive either avanafil tablets 100 mg or sildenafil tablets 50 mg in 1:1 ratio. After 4 weeks of treatment, 40.0% of patients in the avanafil group and 45.6% of patients in the sildenafil group required dose escalation to a high dose (avanafil 200 mg/sildenafil 100 mg). The difference in the mean change of International Index of Erectile Function - Erectile Function score from baseline in the two groups increased from week 4 (1.1, 95% confidence interval -0.2 to 2.5) to week 8 (1.4, 95% confidence interval 0.1-2.7) and week 12 (2.1, 95% confidence interval 0.8-3.5), showing non-inferiority at week 4, and superiority at week 8 and week 12. Avanafil showed a faster onset of action as shown by a significantly better response to modified Sexual Encounter Profile 1 in the avanafil group (84.8%) as compared with that in the sildenafil group (28.2%; P < 0.001). Both avanafil and sildenafil were well tolerated by all the patients in the study; the most common adverse event reported during the study was headache in both the groups.. Avanafil is superior to sildenafil in improving the International Index of Erectile Function - Erectile Function domain score at the end of 12 weeks of treatment with the added advantage of faster onset of action.

Topics: Double-Blind Method; Erectile Dysfunction; Humans; Male; Prospective Studies; Pyrimidines; Sildenafil Citrate; Treatment Outcome

Phosphodiesterase type 5 inhibitors represent the standard treatment of erectile dysfunction after nerve-sparing prostatectomy. Avanafil is a second-generation phosphodiesterase type 5 inhibitor with a high selectivity for phosphodiesterase type 5 isoform. To date, there are no studies comparing the outcomes of avanafil versus sildenafil in this scenario. In this study, we evaluated the efficacy and safety of avanafil versus sildenafil as a drug for post-prostatectomy rehabilitation. Overall, 160 patients submitted to robot-assisted nerve-sparing prostatectomy for localized prostate cancer at three hospitals were enrolled for the present study. After 6 months of treatment, patients in the two groups showed no significantly different sexual function scores, except for the Erection Hardness Score and Sexual Encounter Profile-Q2 that were higher in the Sildenafil group. Adverse events in the Avanafil group occurred in four (5%) patients and in 16 (20%) patients in the Sildenafil group. According to our experience, in patients undergoing nerve-sparing prostatectomy, penile rehabilitation with avanafil compared to sildenafil showed a lower ability to produce a valid erection in the initial phase of sexual intercourse, a difference that disappears in the continuation of the same. Avanafil showed a greater tolerance profile with a lower rate of AEs and discontinuation of therapy due to AEs.

Topics: Aged; Erectile Dysfunction; Humans; Male; Middle Aged; Organ Sparing Treatments; Phosphodiesterase 5 Inhibitors; Postoperative Complications; Prospective Studies; Prostate; Prostatectomy; Prostatic Neoplasms; Pyrimidines; Robotic Surgical Procedures; Sildenafil Citrate; Treatment Outcome

The widespread use of phosphodiesterase-5 inhibitors has attracted broad attention of counterfeiters to develop illicit erectile products with inaccurate amounts, unknown toxicity, and purity of active ingredients. Correspondingly, intake of these products endangers consumer health and needs to be screened for precautionary actions to reduce this risk. Therefore, in this study, a sensitive and rapid analytical method has been developed for simultaneous determination of selected phosphodiesterase-5 inhibitors present in illicit erectile medications and human urine. Quantification of the analytes was performed by liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry system. The chromatographic separation was successfully achieved with a run period of 8 min. Low detection limits were obtained in the range of 1.63-9.81 ng/g with relative standard deviations below 7.72% obtained using the replicate measurements of lowest concentration in calibration plots. The analytical performance of the proposed method proved good linearity, low detection limits, good accuracy and precision with high percent recoveries for human urine samples. Developed method was successfully applied to real samples including four different brands of illicit erectile medications. The results obtained revealed the presence of high levels of sildenafil in analyzed samples. The behaviors of selected phosphodiesterase-5 inhibitors were also studied in simulated gastric conditions.

Topics: Chromatography, Liquid; Erectile Dysfunction; Humans; Illicit Drugs; Male; Pyrimidines; Sildenafil Citrate; Stomach; Tadalafil; Tandem Mass Spectrometry; Vardenafil Dihydrochloride

Topics: Adverse Drug Reaction Reporting Systems; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Phosphodiesterase 5 Inhibitors; Product Surveillance, Postmarketing; Pyrimidines; Retinal Artery Occlusion; Retinal Vein Occlusion; Sildenafil Citrate; Tadalafil; United States; United States Food and Drug Administration; Vardenafil Dihydrochloride

We compared the activity of a new phosphodiesterase-5 inhibitor (PDE5i) avanafil with sildenafil and tadalafil in human and rat corpus cavernosum (CC) tissues. The effect of avanafil with several inhibitors and electrical field stimulation (EFS) was evaluated on CC after pre-contraction with phenylephrine. With the PDE5i, sildenafil and tadalafil, concentration-response curves were obtained and cyclic guanosine monophosphate (cGMP) levels were measured in tissues. Avanafil induced relaxation with maximum response of 74 ± 5% in human CC. This response was attenuated by NOS inhibitor and soluble guanylate cyclase (sGC) inhibitor. Avanafil potentiated relaxation responses to acetylcholine and EFS in human CC and enhanced SNP-induced relaxation and showed 3-fold increase in cGMP levels. When compared with sildenafil, avanafil and tadalafil were effective at lower concentrations in human CC. In addition, Sprague-Dawley rats underwent in vivo intracavernosal pressure (ICP) and mean arterial pressure (MAP) measurements. Avanafil increased ICP/MAP that was enhanced by SNP and cavernous nerve (CN) stimulation in rat CC tissues. Also avanafil showed maximum relaxation response of 83 ± 7% in rat CC with 3-fold increase in cGMP concentration. Taken together, these results of our in vivo and in vitro studies in human and rat suggest that avanafil promotes the CC relaxation and penile erection via NO-cGMP pathway.

Topics: Animals; Blood Pressure; Cyclic GMP; Dose-Response Relationship, Drug; Humans; Male; Penis; Phosphodiesterase 5 Inhibitors; Pyrimidines; Rats; Rats, Sprague-Dawley; Sildenafil Citrate; Tadalafil; Vasodilation

Topics: Aged; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Life Style; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Ion mobility spectrometry was used as a rapid screening tool for the detection of acetildenafils, sildenafils and avanafil within adulterated herbal supplement matrices. Acetildenafils show a tendency for partial fragmentation during the desorption/ionization process affording two peaks in the ion mobility spectrum in addition to the intact compound. The fragmentation appears to occur α to the carbonyl group along the CN bond attaching the piperazine moiety, producing a common fragment (K₀=1.0280 cm²V⁻¹s⁻¹) along with the respective piperazine fragment. The sildenafils and avanafil afford one molecular ion peak per compound.

Topics: Carbolines; Chemistry Techniques, Analytical; Dietary Supplements; Food Contamination; Food Inspection; Imidazoles; Isomerism; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Sildenafil Citrate; Sulfones; Tadalafil; Tandem Mass Spectrometry; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

We evaluated the effects of the highly selective phosphodiesterase type 5 inhibitor avanafil on electroretinogram and hemodynamics in dogs, and compared the effects with those of sildenafil.. Three experiments were performed in anesthetized dogs, including determination of the 1) influence on electroretinogram induced by a light adapted 30 Hz flicker stimulation, 2) direct hemodynamic changes and 3) potentiation of nitroglycerin induced hypotension. Avanafil was administered at doses that were pharmacologically equipotent to or higher than those of sildenafil for penile tumescence.. 1) Intraduodenal doses of avanafil did not influence the electroretinogram waveform. In contrast, sildenafil changed the waveform shape and significantly delayed time to the peak of the electroretinogram positive waveform (vs vehicle p <0.05). 2) Intravenous infusion of avanafil or sildenafil (1 to 300 μg/kg per minute) significantly decreased systemic blood pressure, total peripheral resistance and pulmonary arterial pressure (vs vehicle p <0.05). Administration of sildenafil but not avanafil significantly decreased the resistance of common carotid and vertebral arteries (vs vehicle p <0.05). 3) Intraduodenal doses of avanafil or sildenafil (0.1 and 1 mg/kg) potentiated the AUC of nitroglycerin induced hypotension. However, the potentiating effect of avanafil at 1 mg/kg was significantly weaker than that of sildenafil (p <0.05).. Data suggest that avanafil has a favorable safety profile for erectile dysfunction, which is attributable to its high inhibitory selectivity for phosphodiesterase type 5 against type 6 (retina) and 1 (vessels, etc), respectively, and its short acting pharmacodynamic property.

Topics: Analysis of Variance; Animals; Area Under Curve; Dogs; Electroretinography; Erectile Dysfunction; Hemodynamics; Hypotension; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Retina; Signal Transduction; Sildenafil Citrate; Sulfones

We investigated the in vitro inhibitory effects of avanafil, a novel, potent inhibitor of phosphodiesterase-5, on 11 phosphodiesterases. We also studied its potentiation of penile tumescence in dogs.. Phosphodiesterase assay was done with the 4 phosphodiesterase-5 inhibitors avanafil, sildenafil, vardenafil and tadalafil using 11 phosphodiesterase isozymes. In anesthetized dogs the pelvic nerve was repeatedly stimulated to evoke tumescence. Intracavernous pressure was measured after avanafil or sildenafil administration.. Avanafil specifically inhibited phosphodiesterase-5 activity at a 50% inhibitory concentration of 5.2 nM. Avanafil showed higher selectivity (121-fold) against phosphodiesterase-6 than sildenafil and vardenafil (16 to 21-fold) and showed excellent selectivity (greater than 10,000-fold) against phosphodiesterase-1 compared with sildenafil (375-fold). Avanafil also had higher selectivity against phosphodiesterase-11 than tadalafil (greater than 19,000 vs 25-fold). Avanafil also showed excellent selectivity against all other phosphodiesterases. After intravenous administration in anesthetized dogs the 200% effective dose of avanafil and sildenafil on the penile tumescence was 37.5 and 34.6 μg/kg, respectively. After intraduodenal administration the 200% effective dose of avanafil and sildenafil on tumescence was 151.7 and 79.0 μg/kg at the peak time, respectively. Time to peak response with avanafil and sildenafil was 10 and 30 minutes, respectively, indicating a more rapid onset of avanafil.. Avanafil has a favorable phosphodiesterase-5 selectivity profile compared to that of marketed phosphodiesterase-5 inhibitors. Avanafil shows excellent in vitro and in vivo potency, and fast onset of action for penile erection. Cumulative data suggest that avanafil has a promising pharmacological profile for erectile dysfunction.

Topics: Animals; Carbolines; Dogs; Dose-Response Relationship, Drug; Erectile Dysfunction; Humans; Imidazoles; Infusions, Intravenous; Male; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase type 5 (PDE5) inhibitors are indicated for the treatment of erectile dysfunction (ED); however, they can also inhibit other PDE isozymes, affecting their target tissues (e.g., PDE1: heart; PDE6: retina; and PDE11: skeletal muscle), which in some cases can cause unwanted side effects and therapy discontinuation. Data from in vitro studies showed that avanafil, a PDE5 inhibitor for the treatment of ED, exhibited strong selectivity toward PDE5 and against all other PDE isozymes.. To review the inhibitory effects of avanafil for PDE isozymes compared with those of sildenafil, tadalafil, and vardenafil and to discuss these results within the context of clinical trial safety observations.. Review of in vitro selectivity data for avanafil (published primary data from a peer-reviewed journal and scientific congress abstracts); PubMed search for pertinent publications on PDE5 inhibitor safety data; and review of published articles and abstracts from avanafil phase 1, 2, and 3 clinical trials.. A low incidence of some PDE-related adverse events may be reflected by the high selectivity of avanafil against non-PDE5 isozymes.. Avanafil is highly selective toward PDE5 and against all other PDE isozymes tested. Lower selectivity against PDE1, PDE6, and PDE11 is consistent with results from randomized, placebo-controlled, phase 3 trials in which musculoskeletal and hemodynamic adverse events were reported in <2% of patients and no color vision-related abnormalities were reported with avanafil doses up to 200 mg once daily.. Data suggest that avanafil may confer a safety benefit, in terms of a lower incidence of specific adverse events, by virtue of its high specificity to PDE5 and its overall selectivity against other PDE isozymes.

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride