Zydena is produced for therapy of all male sexual disorders that are characterized by incapacity to achieve or preserve penile erection sufficient for successful sexual intercourse. Zydena contains new active substance belong to the group of PDE5 inhibitors, udenafil.
Zydena Comparison with other PDE5 Inhibitors
Nowadays, international pharmaceutical market has welcomed new selective reversible inhibitor of cyclic guanosine monophosphate-specific PDE5, named Zydena (udenafil). Like other PDE5 inhibitors, Zydena doesn’t take direct relaxing action on isolated cavernous body, but sexual stimulation enhances relaxing effect of nitrogen oxide by means of inhibition of PDE5 which is responsible for decomposition of cyclic guanosine monophosphate in cavernous body that leads to relaxation of smooth muscle cells of arteries and increased blood supply to penile tissues and natural erection. Like other PDE5 inhibitors, Zydena is not effective without sexual stimulation.
Udenafil: What Is It?
Udenafil pharmacological group is organotropic remedies, which means remedies regulating function of urinary system, reproduction and potency regulation. Udenafil is designed for improvement of erectile function. Udenafil is reversible selective inhibitor of cyclic guanosine monophosphate of PDE5. According to research studies, udenafil selectively inhibits enzyme PDE5. This enzyme is present in unstriated muscles of cavernous body and vessels of inner organs, thrombocytes, skeletal muscles, kidneys, lungs and tentorium. As opposed to phosphodiesterase of other types (1, 2, 3, and 4), udenafil is less active by 1000 times than in regards to phosphodiesterase type 5 (PDE5). Other types are located in heart, blood vessels, cerebrum, liver and other organs. Concerning PDE6 that is located in eye retina and responsible for color perception, udenafil is less active by 700 times in comparison with PDE5. Phosphodiesterase type 11 is not affected by udenafil; therefore, pains in back, myodynia, testicular toxicity during udenafil administration are absent.
In half an hour after udenafil intake and with presence of sexual stimulation, the effect occurs. Udenafil action has optimal duration up to 24 hours. It improves erection and possibility of performance of successful coitus. Sound people don’t experience verified changes in diastolic and systolic pressure in lying and upright position in comparison with placebo while taking udenafil. This substance doesn’t cause any alterations in color perception, doesn’t take impact on electroretinogram, sharpness of vision, size of pupil, or intraocular pressure. Also, udenafil doesn’t take any clinically significant action on concentration and quantity of semen, morphology and motility of germ cells.
Udenafil administration is quickly absorbed. Maximal concentration in blood plasma is achieved in 30-90 minutes (generally, in 60 minutes). Elimination half-life is equal to 12 hours; udenafil has a high connectivity rate with blood serum proteins (94%), prolongs the period of its efficiency up to 24 hours after the intake of one dose only. Fatty food or alcohol intake doesn’t influence the absorption rate of udenafil. This substance gets metabolized with participation of isoenzyme CYP3 A4 of cytochrome P450. Total clearance of udenafil in healthy people is equal to 755ml/min. Udenafil is cleared in the form of metabolites with feces. The substance is not accumulated in organism.
Udenafil is indicative to therapy of erectile dysfunction that is characterized by inability to preservation and achievement of erection necessary for fully-realized sexual activity.
Impacts of PDE5 Inhibitors on Cardio-Vascular System
Given PDE5 inhibitors were initially developed for treatment of cardio-vascular system diseases, observation of such medicines’ impacts on cardio-vascular system is constantly required. Clinical research studies and post-marketing examinations of PDE5 inhibitors application didn’t show any occurrence increase of apoplectic attack’s frequency rate on the setting of the therapy conducted. Prescription of PDE5 inhibitors for patients with stable cardiac angina experienced neither training time alteration, not change in ischemia duration during physical activities.
Administration of PDE5 inhibitors, such as udenafil, is strictly contraindicative to men taking nitrates in connection with enhanced probability of hypotension occurrence. Duration of interaction between organic nitrates and PDE5 inhibitors depends on the time of medicines intake. In case of anginal attack after PDE5 inhibitors intake for blocking of the attack instead of nitrates, it is recommended taking medicinal product belonging to another pharmaceutical group; nitrates may be taken only in appropriate time (in 24 hours for sildenafil and vardenafil and in 48 hours for tadalafil). The intake of anti-hypertensive remedies from other pharmaceutical groups doesn’t influence safety profile of PDE5 inhibitors.
During the therapy with PDE5 inhibitors, potential risk of cardio-vascular complications during sexual activity should be taken into account in the following cases: during 3 months after suffered acute myocardial infarction, during 6 months after suffered heart attack, in case of unstable cardiac angina or angina occurred during sexual activity, cardiac failure developed within 6 months, uncontrolled impairments of cardiac rhythm, arterial hypotension or uncontrolled arterial hypertension.
Besides, PDE5 inhibitors are to be taken with caution by patients with underlying risk for priapism (for instance in case of sickle-cell disease, erythroid myeloma or leucosis), as well is by men with anatomic deformation of penis (angulation, cavernous fibrosis, Peyronie’s disease).
Zydena Interaction with Alpha-Adrenoblockers
All PDE5 inhibitors interact with alpha-adrenoblockers differently, which in some cases may lead to occurrence of orthostatic hypotension. Udenafil (Zydena) and medicines from the group of alpha-adrenoblockers are vasodilatory agents; therefore, their combined intake must be prescribed in minimal doses. For instance, sildenafil (Viagra) in the dose of 50mg or 100mg is not recommended to be taken during 4 hours after alpha-adrenoblockers administration. Co-administration of vardenafil (Levitra) with alpha-adrenoblockers is contraindicative either. Nevertheless, according to medical trials, combination of vardenafil with tamsulosin is not associated with clinically significant hypotension. Co-usage of alpha-adrenoblockers with tadalafil (Cialis) is contraindicative as well (excluding tamsulosin).
Zydena is administered perorally regardless of food intake. The drug is applied once a day 30 minutes prior to sexual activity in recommended dose of 100mg of udenafil. In accordance with individual tolerability and effectiveness, udenafil dose may be increased to 200mg. Sexual activity is dangerous for men with pathology of cardio-vascular system; therefore, therapy of erectile dysfunction (including with application of udenafil) is not to be conducted by men suffering from cardiac diseases for whom sexual activity is not recommended. Patients with aortal stenosis causing difficult blood deflux from aortic ventricle may be sensitive to action of vasodilators including PDE inhibitors to a greater extent than patients without this pathology.
During clinical trials of udenafil, the cases of long-term erection (more than 4 hours) or priapism (painful erection lasting more than 6 hours) are not detected. Nevertheless, such complications are characteristic for medications of this class. In case of erection occurrence lasting longer than 4 hours (regardless of presence of pain), patients are required to seek immediate medical attendance. In case of absence of modern therapy of priapism, irreversible damages of erectile tissue and function are possible. Patients older than 71 years of age are not recommended taking udenafil due to absence of clinical data. Zydena is not recommended to be taken along with other types of ED therapy. Zydena should be used with caution by drivers and people whose professions are connected with attention concentration and quickness of psychomotor ability.
Experimental Trials of Udenafil: Study of Pharmacodynamics and Pharmacokinetics
Study of pharmacodynamics
According to clinical trials, Zydena’s active substance, udenafil falls into the group of PDE5 inhibitors. PDE5 is present in smooth muscle cells of cavernous body, unstriated muscles of inner organs, skeletal muscles, thrombocytes, kidneys, lungs and cerebellum. There were held several research studies examining udenafil effects in isolated tissue fragments of rabbit’s unstriated muscles of cavernous bodies. Udenafil caused enhancement of cyclic guanosine monophosphate level that gets increased in presence of nitrogen oxide donor – nitroprussid sodium. These data show that udenafil may enhance erection due to enhancement of muscular relaxation intermediated by nitrogen oxide. Erotogenic action of udenafil is explained by increase of cyclic guanosine monophosphate accumulation in cavernous bodies.
Udenafil is 10000 times stronger inhibitor in regards to PDE5 than regarding PDE1, PDE2, PDE3 or PDE4, that are localized in cerebrum, heart, liver and other organs. Besides, udenafil is 700 times for active in regards to PDE5 than in regards to PDE6 detected in eye retina responsible for color perception. Zydena doesn’t inhibit PDE11 that is explained by absence of myodnia cases, backaches and occurrences of testicular toxicity. The results of pre-clinical research studies have demonstrated high profile of udenafil safety in the class of PDE5 inhibitors.
Study of pharmacokinetics
Pre-clinical studies have shown that Zydena is fast absorbed after peroral intake. The time of maximal concentration in blood serum is 30-90 minutes (in average, 60 minutes). The medicine is characterized by broad distribution in tissues. Udenafil gets metabolized in liver with formation of three metabolites. Peroral introduction of Zydena causes the effect of first passage in liver (decrease of medicine’s exposition by 23% in comparison with intravenous introduction), as well as drug’s transformation in gastro-intestinal tract (exposition reduction by 58%). Udenafil clearance with urine is insignificant.
Elimination half-life is 12 hours; high connectivity rate of Zydena with blood plasma proteins prolongs the period of its efficiency up to 24 hours after one dosage intake (for instance, elimination half-life of sildenafil, vardenafil and tadalafil is 3-5, 4-5 and 17,5 hours accordingly).
Results of Zydena Clinical Trials
During the period between 2001 and 2007, there were held 9 clinical research studies of udenafil (in South Korea, the USA and the UK) with participation of more than 1100 patients. For evaluation of udenafil efficiency, the “golden standard” ED- IIEF was used. In 2005, medical experts conducted double blind placebo-controlled trial with randomized assignment in order to estimate safety, tolerability rate and pharmacokinetics indexes of udenafil after peroral one-time and multiple-time intake by sound Korean men. Experiment comprised 60 men at the age of 19-45 years, where 42 men participated in research of one-time intake of udenafil, whereas 18 – in research of multiple-time intake of the substance.
After one-time udenafil administration in the dose of 25, 50, 100, 200 and 300 mg and many-time intake of udenafil dose 100 and 200mg it was stated that udenafil is fast absorbed, its maximum concentration in organism is achieved within 1-2 hours after the intake regardless of medicine’s dosage; elimination half-life of udenafil is equal to 10-12 hours regardless of medicine’s dose. There was no considerable accumulation of udenafil after 7 days of intake. Main pharmacokinetics parameters, such as elimination half-life and renal clearance remained unchanged after a week of udenafil usage.
Based on all results acquired during clinical trials, it was concluded that Zydena is most efficient in the dose of 100mg. The remedy should be taken perorally 30 minutes before planned sexual intercourse regardless of food intake. Zydena dosage may be enlarged to 200mg in accordance with individual tolerability of the drug. Maximum recommended application frequency is once a day.
According to safety analysis conducted in different countries, the most frequent adverse events connected with udenafil intake are alterations from the part of cardio-vascular system, such as blushing. Also, a patient may experience feeling of heat, nasal congestion, headaches, dyspepsia, discomfort in chest and ocular hyperemia. The rarest side-effects are vertigo, neck muscles rigidity, paresthesia, or blurred vision.