Aim： To examine the preference for two dosing regimens of 20 mg of tadalafil, on demand or three times per week, in men affected with erectile dysfunction （ED） in Italy. Methods： Scheduled Use versus on demand Reg...Aim： To examine the preference for two dosing regimens of 20 mg of tadalafil, on demand or three times per week, in men affected with erectile dysfunction （ED） in Italy. Methods： Scheduled Use versus on demand Regimen Evaluation （SURE） is a multicenter, crossover and open-label study, involving 94 urology centers in Italy. Patients aged 18 years or older affected with ED for at least 3 months were enrolled and randomized to 20 mg of tadalafil treatment on demand or three times per week for 5-6 weeks. After a 1-week washout, patients were crossed over to the alternate regimen for 5-6 weeks. A treatment preference question was used to determine the preferred treatment regimen. International Index of Erectile Function （IIEF） and Sexual Encounter Profile （SEP） questionnaire were used as efficacy measures. Results： A total of 1 058 men （mean age 54.8 years）, were randomized to treatment. Overall, 59.1% of patients preferred the on-demand regimen and 41.9% preferred the three times per week dosing. Both regimens were efficacious and well tolerated. Although a statistically higher improvement of the IIEF erectile function （IIEF-EF） domain score and the SEP questionnaire was reported for the three times per week compared to the ondemand treatment regimen, this difference was numerically minimal and lacking in clinical significance. Conclusion： Tadalafil is effective and well tolerated whether used on demand or three times per week. Patients should be given the option to choose the best treatment regimen according to personal needs and preferences.展开更多
Urotensin-II （U-II） is a cyclic peptide that acts through a G protein-coupled receptor （urotensin-II receptor [UTR]） mainly involved in cardiovascular function in humans. The urotensinergic system is also implicat...Urotensin-II （U-II） is a cyclic peptide that acts through a G protein-coupled receptor （urotensin-II receptor [UTR]） mainly involved in cardiovascular function in humans. The urotensinergic system is also implicated in the urogenital tract. Indeed, U-II relaxes human corpus cavernosum strips and causes an increase in intracavernous pressure （ICP） in rats. In light of this, the U-II/UTR pathway can be considered a new target for the treatment of erectile dysfunction. On this hypothesis, herein we report on two new UTR high affinity-agonists, P5U （H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH） and UPG84（H-Asp-c[Pen-Phe-DTrp-Orn-（pNH2） Phe-Cys]-Val-OH）. The effects of P5U and UPG84 were each compared separately with U-II by monitoring the ICP in anesthetized rats. Intracavernous injection of U-II （0.03-1 nmol）, P5U （0.03-1 nmol） or UPG84 （0.03-1 nmol） caused an increase in ICP. P5U, in particular, elicited a significant increase in ICP as compared to U-II. The observed effect by using P5U at a dose of 0.1 nmol per rat was comparable to the effect elicited by U-II at a dose of 0.3 nmol. Moreover, UPG84 at the lowest dose （0.03 nmol） showed an effect similar to the highest dose of U-II （1 nmol）. Furthermore, UPG84 was found to be more effective than P5U. Indeed, while the lowest dose of P5U （0.03 nmol） did not affect the ICP, UPG84, at the same dose, induced a prominent penile erection in rat. These compounds did not modify the blood pressure, which indicates a good safety profile. In conclusion, UPG84 and P5U may open new perspectives for the management of erectile dysfunction.展开更多
文摘Aim： To examine the preference for two dosing regimens of 20 mg of tadalafil, on demand or three times per week, in men affected with erectile dysfunction （ED） in Italy. Methods： Scheduled Use versus on demand Regimen Evaluation （SURE） is a multicenter, crossover and open-label study, involving 94 urology centers in Italy. Patients aged 18 years or older affected with ED for at least 3 months were enrolled and randomized to 20 mg of tadalafil treatment on demand or three times per week for 5-6 weeks. After a 1-week washout, patients were crossed over to the alternate regimen for 5-6 weeks. A treatment preference question was used to determine the preferred treatment regimen. International Index of Erectile Function （IIEF） and Sexual Encounter Profile （SEP） questionnaire were used as efficacy measures. Results： A total of 1 058 men （mean age 54.8 years）, were randomized to treatment. Overall, 59.1% of patients preferred the on-demand regimen and 41.9% preferred the three times per week dosing. Both regimens were efficacious and well tolerated. Although a statistically higher improvement of the IIEF erectile function （IIEF-EF） domain score and the SEP questionnaire was reported for the three times per week compared to the ondemand treatment regimen, this difference was numerically minimal and lacking in clinical significance. Conclusion： Tadalafil is effective and well tolerated whether used on demand or three times per week. Patients should be given the option to choose the best treatment regimen according to personal needs and preferences.
文摘Urotensin-II （U-II） is a cyclic peptide that acts through a G protein-coupled receptor （urotensin-II receptor [UTR]） mainly involved in cardiovascular function in humans. The urotensinergic system is also implicated in the urogenital tract. Indeed, U-II relaxes human corpus cavernosum strips and causes an increase in intracavernous pressure （ICP） in rats. In light of this, the U-II/UTR pathway can be considered a new target for the treatment of erectile dysfunction. On this hypothesis, herein we report on two new UTR high affinity-agonists, P5U （H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH） and UPG84（H-Asp-c[Pen-Phe-DTrp-Orn-（pNH2） Phe-Cys]-Val-OH）. The effects of P5U and UPG84 were each compared separately with U-II by monitoring the ICP in anesthetized rats. Intracavernous injection of U-II （0.03-1 nmol）, P5U （0.03-1 nmol） or UPG84 （0.03-1 nmol） caused an increase in ICP. P5U, in particular, elicited a significant increase in ICP as compared to U-II. The observed effect by using P5U at a dose of 0.1 nmol per rat was comparable to the effect elicited by U-II at a dose of 0.3 nmol. Moreover, UPG84 at the lowest dose （0.03 nmol） showed an effect similar to the highest dose of U-II （1 nmol）. Furthermore, UPG84 was found to be more effective than P5U. Indeed, while the lowest dose of P5U （0.03 nmol） did not affect the ICP, UPG84, at the same dose, induced a prominent penile erection in rat. These compounds did not modify the blood pressure, which indicates a good safety profile. In conclusion, UPG84 and P5U may open new perspectives for the management of erectile dysfunction.
