Avanafil is a fast-acting, highly selective phosphate diesterase-5 (PDE5) inhibitor, which was approved by the FDA in April 2012. The indication of Avanafil is to treat erectile dysfunction (ED). ED patients can take Avanafil 30 minutes before having sex. This article reviews the pharmacological and pharmacodynamic studies of this drug.
1, Pharmacology Research 
The physiological mechanism of penile erection involves the release of nitric oxide (NO) from the corpus cavernosum during sexual stimulation. Nitric oxide can activate guanylate cyclase, increase the level of cGMP, and then relax the smooth muscle of the corpus cavernosum and make blood flow into the corpus cavernosum. Avanafil has no direct relaxation effect on human cavernous bodies in vitro, but it can inhibit phosphodiesterase-5 (PED5) responsible for the degradation of cGMP content in cavernous bodies by increasing the content of nitric oxide. Because sexual stimulation is a necessary condition for the local release of nitric oxide, the inhibition of PED5 has no effect in the absence of sexual stimulation.
In vitro studies showed that the effect of PED5 was selective. Its effect on PED5 is greater than that of other known phosphodiesterases (100 times stronger than PDE6, 1000 times stronger than PDE4, PDE8, PDE10, 5000 times stronger than PDE2 and PDE7, and 10000 times stronger than PDE1, PDE3, PDE9 and PDE11). PDE6 exists in the retina and is responsible for light transmission. Avanafil has a 100-fold stronger effect on PED5 than PDE6. PDE5 also exists in other tissues, including platelets, blood vessels, visceral smooth muscle, skeletal muscle, brain, heart, liver, kidney, lung, pancreas, prostate, bladder, testis and seminal vesicle. The inhibitory effect of Avanafil on PDE5 in these tissues is based on enhancing NO anti-platelet aggregation activity in vitro and enhancing peripheral vasodilation in vivo.
2, Pharmacodynamics Research
2.1. Effect of Avanafil on Penile Erectile Response 
In a single-blind, placebo-controlled, single-dose clinical trial, 82 patients with organic and/or psychogenic erectile dysfunction received visual stimulation after Avanafil administration, assessed objective stiffness and erectile duration (RigiScan scale) and Placebo improved significantly. 100~120 min was assessed every 20~40 min after administration.
2.2, The Effect Of  On Blood Pressure
The mean systolic/diastolic blood pressure of healthy male volunteers was - 5.3 /- 3.7 mmHg from baseline 1 hour after a single oral dose of Avanafil (200 mg), and the mean systolic/diastolic blood pressure of placebo group was 2.7 /- 0.4 mmHg from baseline. One hour after administration, the systolic/diastolic blood pressure of the 200 mg Avanafil group was 8.0/3.3 mmHg lower than that of the placebo group.
2.3, The Effect On Cardiac Electrophysiology 
A randomized, double-blind, placebo-controlled, active drug (moxifloxacin) cross-over study assessed the effect of a single dose of Avanafil of 100 mg or 800 mg on the QT interval in 52 healthy male subjects aged 18-45 years. 100mg dose had no significant effect. The average QT interval (Fridericia-corrected QT interval) was 9.4 milliseconds (bilateral 90% confidence interval = 7.2, 11.6) in the Avanafil 800 mg dose group compared with the placebo group. A full-scale QT/QT interval trial of healthy male subjects administered with Avanafil (100 mg and 800 mg) showed that Avanafil did not cause any significant changes in the QT interval or ventricular repolarization.
2.4 The Effect Of Combination Of  And Nitroglycerin On Blood Pressure
In clinical pharmacological trials, Avanafil 200 mg showed a similar antihypertensive effect as nitrates. Patients with nitrates used in any dosage form are forbidden to use this method.
An experiment to assess the extent of interaction between Avanafil and nitroglycerin indicated that nitroglycerin should be used in emergencies after taking Avanafil. In a single center, double-blind, randomized three crossover trial, the subjects were healthy men aged 30 to 60 years. The subjects were divided into 5 test groups according to the interval between the test drug and nitroglycerin. Subjects were assigned to each trial group in turn. The severe adverse events (SAE) in the hemodynamic results of the previous trial group were reviewed before the treatment of the next trial group began. Each participant was given three drugs in a random order (Avanafil 200 mg, Sildenafil citrate 100 mg and placebo). Subjects were given nitroglycerin (NTG) 0.4 mg at a predetermined time point (0.5, 1, 4, 8 or 12 hours) after giving the test drug. Overall, 14 placebo-treated subjects (15%) and 28 Avanafil-treated subjects (28%) showed a significant decrease in standing systolic blood pressure after nitroglycerin administration, i.e., standing systolic blood pressure decreased more than or equal to 30 mmHg. The average maximum decrease is shown in the following table. As shown in Table 1.
Similar to other PDE5 inhibitors, the combination of nitrous oxide and nitrite is contraindicated. Patients who have been given Avanafil should be given nitroglycerin at least 12 hours after the last Avanafil treatment if their life is in danger. Under such circumstances, they still need to be taken under the guidance of medical staff and perform hemodynamic monitoring.
2.5, The Effect Of Combination Therapy Of  And Adrenoceptor On Blood Pressure
A single-center, randomized, double-blind, placebo-controlled, two-cycle cross-over study examined the possible interaction between Avanafil and receptor blockers in two groups of healthy male subjects.
Group A (N = 24): The subjects were given doxazosin once a day in the morning at a dose of 1 mg (day 1), 2 mg (day 2-3), 4 mg (day 4-7) and 8 mg (day 8-18). On the fifteenth and 18 days, the subjects were randomly assigned to receive oral mg or placebo once a single time, respectively. On the fifteenth and 18 days, the subjects needed oral administration of 1.3h or placebo after doxazosin administration.
Group B (N=24): subjects received oral tamsulosin hydrochloride 0.4mg (1~11 day) for 11 consecutive days. On the eighth and 11 days, the subjects were randomly assigned to receive oral 200mg or placebo once. On the eighth and 11 days, the subjects needed oral administration of either 3.3 or H oral administration of etanazone or placebo.
Blood pressure and pulse frequency in supine and sitting positions were measured and recorded before or after administration of Avanafil or placebo respectively.
There were 7 subjects in group A whose standing systolic or diastolic blood pressure changed from the absolute value of baseline. The standing systolic pressure of three subjects was less than 85mmHg. A patient's standing systolic blood pressure decreased from baseline to 30mmHg after treatment with a. Two subjects showed standing diastolic pressure less than 45mmHg. In four subjects, the incidence of standing diastolic blood pressure dropped to more than 20mmHg after giving ATV. A placebo-controlled diastolic blood pressure dropped more than 20mmHg after giving placebo. No serious adverse reactions related to hypotension were reported during the trial. No case developed syncope.
There were 5 subjects in group B (Tamsulosin hydrochloride group) whose standing systolic or diastolic blood pressure changed from baseline absolute value or had clinical significance. The mean systolic blood pressure of two subjects was less than 85mmHg after the treatment. A patient's standing systolic blood pressure decreased from baseline to 30mmHg after treatment with a. Two subjects had a standing diastolic pressure of less than 45mmHg after giving ATV. Four subjects had a standing diastolic blood pressure drop greater than 20 mmHg after administering Avanafil, and one subject had a standing diastolic blood pressure drop greater than 20 mmHg after administering placebo. No serious adverse reactions related to hypotension were reported during the trial. No case developed syncope.
The table below shows the average maximum decrease in systolic blood pressure (95% confidence interval) from baseline in the placebo group of 24 subjects who received 200 mg of Avanafil and placebo.
2.6, The Effect Of Combination Therapy Of Alfa And Enalapril On Blood Pressure.
The average maximum reduction of supine systolic/diastolic blood pressure was 1.8/3.5 mHg (compared with placebo) after a single dose of Avanafil 200 mg combined with Enalapril, accompanied by an average maximum increase of 1.0 BPM in pulse rate.
2.7, The Effect Of Combination Of Acnnac And Amlodipine On Blood Pressure.
The average maximum reduction of supine systolic pressure was 1.2 mmHg (compared with placebo) after single dose of Avanafil 200 mg combined with amlodipine, accompanied by an average maximum increase of 1.0 BPM in pulse rate, and the average maximum reduction of diastolic pressure was significantly lower than that in placebo group. There was no effect on the plasma concentration of amlodipine. After treatment with amlodipine, the Cmax and AUC of acnnir increased by 22% and 70% respectively.
2.8, The Effect Of  On The Blood Pressure At The Same Time.
A clinical pharmacology experiment has evaluated the interaction between alpha and non alcoholic. At the same time, 200mg was administered with 0.5g/kg at the same time. The blood alcohol content was confirmed to be 0.057%. No report of orthostatic hypotension or dizziness. When Avanafil was administered concurrently with alcohol, the maximum systolic/diastolic blood pressure decreased by 3.5/4.5mmHg in supine position and the maximum increase in pulse frequency was 9.3 bpm. This effect did not affect blood alcohol concentration.
2.9, The Effect Of This Effect On Semen.
In a group of healthy male subjects, the single dose of Avanafil 200 mg had no acute toxic effect on sperm motility and sperm morphology.
2.10, The Effect Of Acv On Vision.
A single oral administration of phosphodiesterase 5 inhibitors can cause a temporary decrease in color discrimination (blue/green). Farnsworth-Munsell 100 chromaticity test showed that the decrease was dose-dependent and had the greatest impact on the time when the plasma concentration reached its peak. This finding is consistent with the inhibitory effect of PDE6 on retinal photoconduction.
3.1, carcinogenic test
CD-1 mice were given 100, 200, 600 mg/kg daily for at least 98 weeks, and SD rats were given 100, 300, 1000 mg/kg daily for at least 100 weeks. Both tests showed that Avanafil had no carcinogenic effect.
3.2, Mutagenicity Test
Ames test showed that there was no mutagenic effect of this drug. Chromosome aberration test of Chinese hamster ovary cells and lung cells and micronucleus test in mice showed that Avanafil had no mutagenic effect. Rat non procedural DNA synthesis test showed that atorvastatin did not affect DNA repair.
3.3, Reproductive Toxicity
In a study of rat reproductive capacity and early embryonic development, male rats were given 100, 300, 1000 mg/kg daily from 28 days before mating to euthanasia, and female rats were given 100, 300, 1000 mg/kg daily from 14 days before mating to 7 days after pregnancy, without any decrease in sperm motility or change in estrus. The percentage of abnormal sperm (sperm head rupture) increased when the exposure of male rats was about 11 times that of humans after 200 mg.
ED has become one of the most important diseases afflicting men worldwide. About 150 million men worldwide have different degrees of ED. As a newly listed high selective PDE5 inhibitor, pharmacodynamics of Avanafil showed that Avanafil could selectively act on PED5, which could significantly improve penile erectile response and had a short acting time.