Mirodenafil

Mirodenafil is a drug used for the treatment of erectile dysfunction (ED).

The basic pharmacological profile, including the mechanism of action, dosage, adverse effects, safety, drug interactions, history, and relevant studies, will be described in this article.

What Is Mirodenafil?

Mirodenafil is a potent, reversible, and selective oral PDE5 inhibitor used to treat erectile dysfunction.

Clinical studies have revealed that mirodenafil has ten times more affinity and selectivity for PDE5 than sildenafil [1]. Its affinity for the PDE5 receptor to other PDE5 inhibitors is still higher than sildenafil, tadalafil, and vardenafil leading to adverse effects like flushing, headache, and tachycardia.

Mirodenafil is beneficial for ED in diabetics and patients with lower urinary tract symptoms/ BPH [2].

What Is the Dose of Mirodenafil?

It is available as:

• Oral tablets 50 mg and 100 mg
• Orally dissolving film 50 mg

Both 50 mg and 100 mg doses are well-tolerated and effective for erectile dysfunction in multiple studies [1].

How Long Does It Take to Kick In?

It takes around 40 to 60 minutes for the drug to work. However, it requires sexual excitement to work. You should take one pill at least half to one hour before sexual activities.

How Long Does It Last?

It lasts for 2.5 to 3 hours, shorter than other drugs of the same category.

History of Mirodenafil

Mirodenafil was developed in 2007 by SK Chemicals Life Science and is marketed only in Korea.

Several clinical trials have been conducted on mirodenafil, but it has not been approved by the FDA. Further well-designed studies with larger cohorts of different ethnicities, flexible dosing schedules, and long-term follow-up are necessary to evaluate its efficacy and tolerability profiles for the treatment of ED.

Is It Safe? What Are Its Side Effects?

Most studies conducted with mirodenafil show it is effective, well-tolerated, and safe [3, 4, 12].

During the trials, the major side effects seen were:

• Diarrhea
• Dizziness
• Dyspepsia
• Facial flushing
• Headache
• Nasal congestion
• Tachycardia

Drug Interactions With Mirodenafil

Many drugs interact with PDE5 inhibitors, so check with your doctor before combining mirodenafil with any of the following.

Nitrates

PDE5 inhibitor use is contraindicated with nitrates as they may act synergistically and enhance the hypotensive effects. However, there are no studies on the specific relationship of mirodenafil with nitrates.

Guanylate Cyclase (GC) Stimulators

Avoid using PDE5 inhibitors with GC stimulators, as they can interact and rapidly drop blood pressure. However, there are no individual studies about the interaction between mirodenafil and GC stimulators.

Anti-Hypertensives

On-demand mirodenafil combined with antihypertensives improves erectile dysfunction without significant changes in hypertension-associated parameters such as blood pressure, heart rate, or ECG findings. This finding was established by a randomized, placebo-controlled clinical trial in patients taking an antihypertensive drug [5].

However, there was a relatively small percentage of patients taking diuretics (14.8%) and a beta-adrenergic blocker (25.9%), and the immediate effects were not evaluated.

Alcohol

According to a study [7], mirodenafil with alcohol did not cause clinically significant hemodynamic changes.

Antacids

Common antacids can reduce the absorption of mirodenafil from the gastrointestinal tract.

CYP3A4 Inducers

These medications increase the enzyme activity, leading to faster metabolism of mirodenafil and shorter, less pronounced effects.

Some common CYP3A4 inducers include rifampin, carbamazepine, phenytoin, and phenobarbitone.

CYP3A4 Inhibitors

Mirodenafil undergoes extensive biotransformation in human liver microsomes, mainly via cytochrome P450 (CYP3A4), with a minor contribution from CYP2C. According to a study [6], co-administration of CPY3A4 inhibitors with mirodenafil results in an increased half-life of the latter.

Dapoxetine

A study of mirodenafil combined with dapoxetine in patients with premature ejaculation (PE) without ED has been published [8]. The results suggested that adding a PDE5 inhibitor to dapoxetine may be more effective and safer than dapoxetine alone.

Who Should Avoid Mirodenafil?

Patients with any of the following should avoid mirodenafil:

• Cerebrovascular disease
• Hypersensitivity to any PDE5 inhibitor drugs
• NAION or “crowded” optic disc
• Priapism
• Retinitis pigmentosa
• Severe heart disease
• Severe kidney disease (requires dose alteration)
• Using drugs like nitrates and GC stimulators

How Does Mirodenafil Work?

Mirodenafil is a PDE5 inhibitor. It acts as a competitive inhibitor of the enzyme phosphodiesterase type 5 (degradative action on cGMP) in the smooth muscle cells lining the blood vessels, increasing cGMP concentration.

It is a part of the Nitric Oxide/Guanine Cyclase/cGMP pathway. Nitric Oxide (NO) is released at high levels from endothelial cells and penile nerves during sexual stimulation. NO then diffuses to the nearby vascular smooth muscles, where it activates the GC, which converts GTP to cGMP.

Mirodenafil increases the cGMP levels, increasing the blood flow to the corpus cavernosum, leading to penile erection.

In simple words, the drug dilates the blood vessels around the penis, leading to increased blood flow and erection. The drug requires sexual arousal to work, so it is taken before having sex.

Alternatives To Mirodenafil

There are many ED medications, some using the same active ingredient, others with different ingredients that share the same mechanism of action.

Mirodenafil is a generic medication, which means it’s also manufactured by lots of other companies — some cheaper, some more expensive, but for the most part, the same compound.

The most widely used PDE5 inhibitor prescription drug is sildenafil, commonly known as Viagra.

Pharmaceutical Alternatives

• Avanafil (Avaforce, Stendra, Avana)
• Sildenafil (Viagra, Cenforce, Kamagra, Fildena, P-Force, Vygex, & more)
• Tadalafil (Cialis, Adcirca, Vidalista, Tadacip, Forzest, & more)
• Vardenafil (Levitra, Staxyn, Vilitra, Zhewitra, Savitra, & more)

Natural Alternatives

There are some herbs and nutrients that can also help facilitate erection. These are better to start with than prescription medications. If they don’t work, then move up to pharmaceutical options. These herbal compounds are effective but also have side effects.

Horny Goat Weed (Epimedium spp.)

It has been used for ED for years.  Italian researchers found that the main compound in horny goat weed, called icariin, acted similarly to drugs like sildenafil.

Ginseng (Panax ginseng)

Studies show the benefit of Korean red ginseng for ED [9, 10]. It is believed to work by inducing the release of NO and relaxation of smooth muscles of the corpus cavernosum.

L-arginine

A study in the Journal of Sex and Marital Therapy found that L-arginine and Pycnogenol supplements helped many men ages 25 to 45 with ED achieve normal erections. The treatment also didn’t cause side effects with ED medication [11].

Muira Puama (Ptychopetalum olacoides)

This herb is used for libido and penile erections. It is rich in sitosterol, campesterol, and lupeol and helps boost testosterone, restoring sex drive and improving performance.

Catuaba (Erythroxylum catuaba)

Catuaba extract is a central nervous system stimulant used in some Asian remedies for low libido.

Yohimbe (Pausinystalia yohimbe)

Yohimbe improves vasodilation and acts as a monoamine oxidase inhibitor, increasing serotonin in the brain. It acts as an aphrodisiac but can cause anxiety in some people.

Tribulus (Tribulus terrestris)

It improves sexual activity by increasing the levels of testosterone and NO synthesis.

Medical Research Involving Mirodenafil

There have been multiple studies on the drug in small cohorts, but studies regarding the interaction of the drug with other drugs are limited.

Here’s the summary of some prominent clinical studies on mirodenafil over the years:

Efficacy & Safety of Mirodenafil for Erectile Dysfunction

A clinical trial placed 223 Korean men with a broad range of ED in a randomized study group and a placebo-control group. The control group was given a fixed dose of mirodenafil of 50 mg and 100 mg for 12 weeks on an “as-needed” basis [12].

At the end of the study, researchers reported that the control group showed significant improvement in both sexual life and partner relationships than the placebo group. Most treatment-associated adverse effects were of mild intensity and resolved spontaneously.

Where To Buy Mirodenafil?

Mirodenafil is only marketed in Korea and is not available in other countries.

Other drugs (sildenafil, tadalafil, vardenafil, avanafil) are available with a doctor’s prescription. Consult your doctor before using these drugs for better efficacy and safety.

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References

1. Cho, M. C., & Paick, J. S. (2016). A review of the efficacy and safety of mirodenafil in the management of erectile dysfunction. Therapeutic advances in urology, 8(2), 100-117.
2. Bang, W. J., Oh, C. Y., Yoo, C., Cho, J. S., Yang, D. Y., Lee, D. H., … & Chung, B. H. (2013). Efficacy and safety of the simultaneous administration of mirodenafil and an α-blocker in men with BPH-LUTS: a multicenter open-label prospective study. International journal of impotence research, 25(4), 149-154.
3. Chung, J. H., Kang, D. H., Oh, C. Y., Chung, J. M., Lee, K. S., Kim, T. H., … & Lee, S. W. (2013). Safety and efficacy of once daily administration of 50 mg mirodenafil in patients with erectile dysfunction: a multicenter, double-blind, placebo controlled trial. The Journal of urology, 189(3), 1006-1013.
4. Reyes-García, J. G., Santos-Caballero, N., & Flores-Murrieta, F. J. (2016). Safety and Efficacy of Oral Mirodenafil in Mexican with Erectile Dysfunction. International Journal of Clinical Medicine, 7(09), 628.
5. Paick, J. S., Kim, J. J., Kim, S. C., Moon, K. H., Min, K. S., Park, K., … & Yang, D. Y. (2010). Efficacy and safety of mirodenafil in men taking antihypertensive medications. The journal of sexual medicine, 7(9), 3143-3152.
6. Shin, K. H., Kim, B. H., Kim, T. E., Kim, J. W., Yi, S., Yoon, S. H., … & Yu, K. S. (2009). The effects of ketoconazole and rifampicin on the pharmacokinetics of mirodenafil in healthy Korean male volunteers: an open-label, one-sequence, three-period, three-treatment crossover study. Clinical therapeutics, 31(12), 3009-3020.
7. Kim, B. H., Yi, S., Kim, J., Lim, K. S., Kim, K. P., Lee, B., … & Yu, K. S. (2009). Influence of alcohol on the hemodynamic effects and pharmacokinetic properties of mirodenafil: a single-dose, randomized-sequence, open-label, crossover study in healthy male volunteers in Korea. Clinical therapeutics, 31(6), 1234-1243.
8. Lee, W. K., Lee, S. H., Cho, S. T., Lee, Y. S., Oh, C. Y., Yoo, C., … & Yang, D. Y. (2013). Comparison between on‐demand dosing of dapoxetine alone and dapoxetine plus mirodenafil in patients with lifelong premature ejaculation: Prospective, randomized, double‐blind, placebo‐controlled, multicenter study. The journal of sexual medicine, 10(11), 2832-2841.
9. De Andrade, E., De Mesquita, A. A., de Almeida Claro, J., De Andrade, P. M., Ortiz, V., Paranhos, M., … & Erdogrun, T. (2007). Study of the efficacy of Korean Red Ginseng in the treatment of erectile dysfunction. Asian journal of andrology, 9(2), 241-244.
10. Hong, B., Ji, Y. H., Hong, J. H., Nam, K. Y., & Ahn, T. Y. (2002). A double-blind crossover study evaluating the efficacy of korean red ginseng in patients with erectile dysfunction: a preliminary report. The Journal of urology, 168(5), 2070-2073.
11. Stanislavov, R., & Nikolova, V. (2003). Treatment of erectile dysfunction with pycnogenol and L-arginine. Journal of Sex &Marital Therapy, 29(3), 207-213.
12. Paick, J. S., Ahn, T. Y., Choi, H. K., Chung, W. S., Kim, J. J., Kim, S. C., … & Jung, H. G. (2008). ED PHARMACOTHERAPY: Efficacy and Safety of Mirodenafil, A New Oral Phosphodiesterase Type 5 Inhibitor, for Treatment of Erectile Dysfunction. The journal of sexual medicine, 5(11), 2672-2680.
13. Park, H. J., Moon, K. H., Lee, S. W., Lee, W. K., Kam, S. C., Lee, J. H., & Park, N. C. (2014). Mirodenafil for the treatment of erectile dysfunction: a systematic review of the literature. The World Journal of men’s health, 32(1), 18-27.
14. Cho, M. C., & Paick, J. S. (2016). A review of the efficacy and safety of mirodenafil in the management of erectile dysfunction. Therapeutic advances in urology, 8(2), 100-117.