AB030. Evolution of phosphodiesterase type 5 inhibitors

Abstract: After launching of sildenafil citrate, the last invention of 20^th century, in 1998, oral phosphodiesterase type 5 (PDE5) inhibitor has been established as first line treatment of erectile dysfunction and shift new paradigm of diagnosis and treatment of erectile dysfunction. The big success of sildenafil in pharmaceutical R&D induced the consecutive development of the so-called ‘The second Viagra’, e.g., tadalafil and vardenafil in 2003. Currently, these 3 kinds of PDE5 inhibitors are most famous and well-known PDE5 inhibitors worldwide. From the early competition, PDE5 inhibitors have been continuously evolved through completion for survival. In Korea, another 3 kinds of PDE5 inhibitors, udenafil [2005], mirodenafil [2007] and avanafil [2011] have been developed. Additionally 60 generic sildenafils from 49 companies were released with termination of sildenafil patent in Korea, 2012 and 160 generic tadalafils from 64 companies were released with termination of tadalafil patent in Korea, 2015. Besides of Korea PDE5I, generic sildenafil and generic tadalafil induce cheaper PDE5I, as much as 1/5 of original PDE5Is. The dosage concept also evolved from on-demand to daily low-dose and alternative dosage. These changes of dosage concept was proved from safety of daily use and indication of PDE5Is for ED also evolved beyond ED and widened to pulmonary hypertension of Sildenafil, benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) of tadalafil and penile rehabilitation after RRP. For the launching of Generic PDE5Is, the preparation also evolved from tablet to orodisposable film, granule and chewable. The orodisposable film and chewable is favorable from patients. In Korea, the impact of recent generic tadalafil is totally different from those of generic Sildenafil in 2012. The long half-life of tadalafil enabled the approval for BPH/LUTS with daily low dose usage. In turn, the generic Cialis also will be developed as various preparations including orodisposable film and as combination with antihypertensive for ED/HT, PDE5 inhibitor with alpha blockers for ED/LUTS and PDE5 inhibitor with antidepressant for ED/PE. Since the launching of sildenafil citrate in 1998, the PDE5 inhibitors have been evolved into various drugs including generics, change of dosage concept, widened indication beyond ED and various preparations. From now, various forms of combination drugs will be emerged for cross risk factor treatment, reduction of pill burden and price, and eventual ED prevention and cure.

Keywords: Phosphodiesterase type 5 (PDE5) inhibitor; erectile dysfunction (ED); lower urinary tract symptoms (LUTS); premature ejaculation (PE)