Efficacy and Tolerability of Lodenafil Carbonate for Oral Therapy in Erectile Dysfunction: A Phase II Clinical Trial

Abstract

Introduction Oral treatment with phosphodiesterase type 5 inhibitor (PDE5) is considered the first-line treatment for patients with erectile dysfunction (ED). Lodenafil carbonate (LC) is a novel PDE5. Aim This is a phase II, prospective, randomized, double-blind, and placebo controlled clinical trial of LC. Main Outcome Measures Efficacy end points were International Index of Sexual Function (IIEF) erectile domain, IIEF questions 3 and 4, and Sexual Encounter Profile (SEP) questions 2 and 3, before and after the use of LC or placebo. Methods Seventy-two men older than 18 years, with ED for at least 6 months with stable sexual relationship were enrolled. Patients were randomized to placebo or LC 80 mg, 40 mg, or 20 mg and followed for 4 weeks. Results IIEF erectile domain scores before and after the use of medications were (mean ± standard deviation [SD]): placebo: 11.9 ± 3.4 and 12.6 ± 5.5; LC 20 mg: 15.8 ± 4.1 and 18.9 ± 6.6; LC 40 mg: 11.9 ± 4.4 and 15.4 ± 8.1; LC 80 mg: 14.2 ± 4.7 and 22.8 ± 6.0 (anovaP < 0.01). The SEP-2 scores before and after the use of medications were (Mean ± SD): placebo: 71.0 ± 33.1 and 51.2 ± 43.1; LC 20 mg 70.3 ± 34.2 and 75.5 ± 31.5; LC 40 mg: 48.4 ± 42.1 and 60.8 ± 42.5; LC 80 mg: 68.6 ± 33.5 and 89.6 ± 26.0. The SEP-3 scores were: placebo 23.3 ± 27.6 and 33.6 ± 42.3; LC 20 mg: 32.3 ± 38.9 and 51.2 ± 41.7; LC 40 mg: 39.7 ± 44.7 and 46.7 ± 41.1; LC 80 mg* 17.2 ± 29.5 and 74.3 ± 36.4 (*P < 0.05 for difference to placebo). Conclusions The drug was well tolerated. Adverse reactions were mild and self-limited and included headache, rhinitis, flushing, color visual disorders, and dyspepsia. This study showed that the dosage of 80 mg of LC was significantly more efficacious than placebo and well tolerated.

A review of analytical methods for the determination of four new phosphodiesterase type 5 inhibitors in biological samples and pharmaceutical preparations

“…Figure 2) has a unique chemical structure; a carbonate bridge unites 2 molecules of lodenafil. After ingestion the carbonate bridge is broken freeing each molecule of lodenafil for biologic effect (Glina et al, 2010;Toque et al, 2010;McNamara;Donatucci, 2011).…”

“…For oral administration with a 600 kcal lipid meal, the parameters were: Cmax = 148 ng/mL; Tmax = 3.1 h; T1/2 = 2.63 h; AUC = 683 ng h/mL. Therefore, administration with lipids delayed the absorption but increased the bioavailability (Lucio et al, 2007;Glina et al, 2010).…”

“…Lodenafil carbonate (Helleva ® ) is PDE5i developed in Brazil. It is a dimer that acts as a prodrug delivering lodenafil in vivo (Toque et al, 2008;Glina et al, 2009).…”

New treatments for erectile dysfunction

“…However, more reports of headache, flushing, rhinitis, dizziness and visual disturbance occurred on lodenafil relative to placebo. 15 • Mirodenafil is a potent and selective inhibitor of cGMPspecific PDE-5. A meta-analysis of three multi-centre, randomised, double-blind, placebo-controlled clinical trials involving 374 patients revealed that mirodenafil was found to be effective and well-tolerated over 12 weeks of treatment.…”

Current Perspectives on Pharmacotherapy Treatments for Erectile Dysfunction

“…After ingestion, the carbonate bridge is broken delivering the active lodenafil compound [8,25]. The effects of lodenafil have been extensively investigated in vitro; the drug was noted to cause concentration-dependent relaxation of both rabbit and human corpus cavernosum tissue by amplifying the NOdependent relaxation of the penile tissue in response to acetylcholine or transmural electrical field stimulation (EFS) [8].…”