Zydena Mechanism of Action

Pharmacology: Pharmacodynamics: Zydena is an oral therapy for the treatment of erectile dysfunction, the fourth entrant to the global erectile dysfunction market and first by a Korean pharmaceutical company.
Zydena, an oral therapy for erectile dysfunction, is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) of the corpus cavernosum.
Mechanism of Action: The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum and allowing inflow of blood.
NO activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth relaxation in the corpus cavernosum and allowing inflow of blood.
Udenafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum.
Udenafil at recommended dose has no effect in the absence of sexual stimulation.
Studies in vivo have shown that Udenafil is selective for PDE5.
Clinical studies: Zydena demonstrated 88.5% improvement in patients with erectile dysfunction.
Based on the results from the phase III trial performed in 13 Korean centers for up to 6 months in duration, Zydena, compared to placebo, showed 81.5% and 88.5% improvement in Global Assessment Questionnaire (GAQ) scores at doses of 100 and 200 mg, respectively, in 270 erectile dysfunction patients.
The efficacy and safety data of Zydena were satisfactory in all of the phase I, II, and III trials performed in Korea.
Zydena is a unique oral therapy for the treatment of erectile dysfunction, which has completed its entire clinical trial processes in Korea. The major adverse events are flushing, nasal congestion, headache, and dyspepsia. However, most adverse events were temporal and mild in severity, which soon resolved without treatment.
Zydena does not inhibit phosphodiesterase type 11 (PDE11) (>3,000-fold selectivity) and adverse effects such as myalgia, back pain, and testicular toxicity, etc. have not been reported.
Zydena does not inhibit phosphodiesterase type 11 (PDE11) and adverse events such as myalgia, back pain, and testicular toxicity were not observed in clinical trials.
Pharmacokinetics: Zydena has an optimal duration of action of up to 8 to 12 hours.
Clinical pharmacokinetic study showed that the time to maximum concentration (Tmax) and half-life (T_½) of Zydena are approximately 1 hour and 10 to 12 hours, respectively. The ability to maintain an erection sufficient for a successful intercourse (SEP3) at 8 to 12 hours after taking Zydena (100 mg) was significantly superior to placebo in phase III trial. The duration of action was neither too short nor long, and was considered appropriate.
Pharmacokinetics in special patient groups: Elderly: Zydena (100 mg) was administered once to 12 healthy elderly (age 65 to 80 years) and 12 young adults (age 19 to 45 years) in the pharmacokinetic properties and safety comparative evaluation clinical trial. The plasma peak concentration and AUC of Zydena were 0.73 times and 0.88 times lower, respectively, in elderly patients compared to the young adults. Thus, as it is unlikely that the systemic exposure of Zydena will be increased when used in the elderly, no dosage adjustment is necessary.
Renal Impairment: The pharmacokinetic characteristics and safety were compared and evaluated in a clinical trial where Zydena 100 mg was administered for single therapy in 9 healthy male subjects, 9 patients with mild renal impairment (creatinine clearance rate 50~80 mL/min), 6 patients with moderate renal impairment (creatinine clearance rate 30~50 mL/min), and 7 patients with severe renal impairment (creatinine clearance rate < 30 mL/min). The exposure of Zydena (AUC) was increased compared to healthy male subjects by 1.3 times in case of mild renal impairment and approximately 1.6 times in case of moderate or severe renal impairment. Information on terminal stage renal failure patients undergoing dialysis is unknown.
Hepatic Impairment: The pharmacokinetic characteristics and safety were compared and evaluated in a clinical trial where Zydena 100 mg was administered for single therapy in 6 healthy male subjects, 6 patients with mild hepatic impairment (Child-Pugh Class A) and 6 patients with moderate hepatic impairment (Child-Pugh Class B). The exposure of Zydena (AUC) was increased compared to healthy male subjects by 1.05 times in case of mild hepatic impairment and 1.49 times in case of moderate hepatic impairment. There is no information on administering more than Zydena 100 mg in patients with hepatic impairment.