Oral Pharmacokinetics of Mirodenafil in Mexican Healthy Volunteers

Miriam del Carmen Carrasco-Portugal, Francisco Javier Flores-Murrieta, Juan Gerardo Reyes-García, Noemí Santos-Caballero

Landsteiner Scientific, S.A. de C.V., México DF, México.
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México DF, México.
Unidad de Investigación en Farmacología, Insituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, México DF, México.
Unidad de Investigación en Farmacología, Insituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, México DF, México; Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México DF, México.

DOI: 10.4236/pp.2014.51016                

Abstract

Mirodenafil is a 5-phosphodiesterase inhibitor that is currently marketed in Korea for the treatment of erectile dysfunction; however, no information in other populations is available. It has been described that Mirodenafil is metabolized by CYP3A4, a metabolic pathway in which interethnic differences have been reported. The purpose of this study was to characterize the oral pharmacokinetics of Mirodenafil in Mexicans. Seventeen male healthy volunteers were enrolled in this study. After an overnight fast, volunteers received an oral 100 mg dose and blood samples were collected at selected times during 24 h. Plasma was stored frozen and analyzed by an HPLC method. Pharmacokinetic parameters obtained were: C_max 331.129 ± 32.689 ng/mL, t_max 1.574 ± 0.293 h, AUC_24h 883.293 ± 104.088 ng·h/mL, AUC_￥ 976.477 ± 108.812 ng·h/mL and t_1/2 1.807 ± 0.171 h. Parameter values observed in this study are similar to those reported in Koreans. Since efficacy and safety studies of Mirodenafil have been conducted in Koreans, it is expected that dosage regime to employ in Mexicans should be similar to the approved for Korean population.

Keywords

Erectile Dysfunction; Healthy Volunteers; Mexican; Mirodenafil; Pharmacokinetic

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	J. S. Paick, T. Y. Ahn, H. K. Choi, et al., “Efficacy and Safety of Mirodenafil, a New Oral Phosphodiesterase Type-5 Inhibitor for Treatment of Erectile Dysfunction,” Journal of Sexual Medicine, Vol. 5, No. 11, 2008, pp. 2672-2680. http://dx.doi.org/10.1111/j.1743-6109.2008.00945.x
[2]	C. C. Carson and T. F. Lue, “Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction,” BJU International, Vol. 96, No. 3, 2005, pp. 257-280. http://dx.doi.org/10.1111/j.1464-410X.2005.05614.x
[3]	J. D. Corbin and S. H. Francis, “Pharmacology of Phosphodiesterase-5 Inhibitors,” International Journal of Clinical Practice, Vol. 56, No. 6, 2002, pp. 453-459.
[4]	G. Lee, T. K. Kim and B.Y. Lee, “Pharmacokinetics of Mirodenafil, a New Erectogenic, and Its Metabolite, SK 3541, in Rats: Involvement of CYP1A1/2, 2B1/2, 2D Subfamily, and 3A1/2 for the Metabolism of Both Mirodenafil and SK3541,” Journal of Pharmacy & Pharmaceutical Sciences, Vol. 13, No. 1, 2010, pp. 93-106.
[5]	H. Kim, D. W. Sohn, S. D. Kim, S. H. Hong, H. J. Suh, C. B. Lee and S. W. Kim, “The Effect of Mirodenafil on the Penile Erection and Corpus Cavernosum in the Rat Model of Cavernosal Nerve Injury,” International Journal of Impotence Research, Vol. 22, No. 5, 2010, pp. 291-297. http://dx.doi.org/10.1038/ijir.2010.19
[6]	S. K. Lee, Y. Kim, T. K. Kim, G. J. Im, B. Y. Lee, D. H. Kim, C. Jin and H. H. Yoo, “Determination of Mirodenafil and Sildenafil in the Plasma and Corpus Cavernous of SD Male Rats,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 49, No. 2, 2008, pp. 513-518. http://dx.doi.org/10.1016/j.jpba.2008.11.004
[7]	Y. S. Lee, Y. H. Choi, S. Y. In, T. K. Kim, K. H. Ryu, B. Y. Lee and M. G. Lee, “Pharmacokinetics of Mirodenafil and Its Two Metabolites, SK3541 and SK3544, in Spontaneously or DOCA—Salt-Induced Hypertensive Rats,” Biopharmaceutics & Drug Disposition, Vol. 32, No. 1, 2011, pp. 38-49. http://dx.doi.org/10.1002/bdd.737
[8]	B. S. Shin, S. K. Hu, J. Kim, J. G. Oh, W. N. Youn, B. Lee, K. A. Um, D. K. Kim, J. Y. Lee and S. D. Yoo, “Development of LC/MS/MS Assay for the Determination of 5-ethyl-2-{5-[4-(2-Hydroxyethyl)Piperazine-1-Sulfonyl]-2-Propoxyphenyl}-7-Propyl-3,5-Dihydropyrrolo [3, 2-d]Pyrimidin-4-One (SK3530) in Human Plasma: Application to a Clinical Pharmacokinetic Study,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 45, No. 1, 2007, pp. 176-184. http://dx.doi.org/10.1016/j.jpba.2007.06.021
[9]	B. H. Kim, S. Jeong, J. W. Kim, K. Lim, K. P. Kim, B. Y. Lee, S. G. Shin, I. J Jang and K. S. Yu, “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, Vol. 31, No. 12, 2009, pp. 1234-1243. http://dx.doi.org/10.1016/j.clinthera.2009.06.008
[10]	K. H. Shin, B. H. Kim, T. E. Kim, J. W. Kim, S. J. Yi, S. H. Yoon, J. Y. Cho, S. G. Shin, I. J. Jang and K. S. Yu, “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, Vol. 31, No. 12, 2009, pp. 3009-3020. http://dx.doi.org/10.1016/j.clinthera.2009.12.012
[11]	G. Castañeda-Hernández, C. Hoyo-Vadillo, J. A. Palma-Aguirre and F. J. Flores-Murrieta, “Pharmacokinetics of Oral Nifedipine in Different Populations,” Journal of Clinical Pharmacology, Vol. 33, No. 2, 1993, pp. 140-145. http://dx.doi.org/10.1002/j.1552-4604.1993.tb03934.x
[12]	J. A. Palma-Aguirre, J. González-Llaven, F. J. Flores-Murrieta and G. Castañeda-Hernández, “Bioavailability of Oral Cyclosporine in Healthy Mexican Volunteers: Evidence for Interethnic Variability,” Journal of Clinical Pharmacology, Vol. 37, No. 7, 1997, pp. 630-634. http://dx.doi.org/10.1002/j.1552-4604.1997.tb04346.x
[13]	L. Chávez-Teyes, G. Castañeda-Hernández and F. J. Flores-Murrieta, “Pharmacokinetics of Midazolam in Mexicans: Evidence for Interethnic Variability,” Clinical Drug Investigation, Vol. 17, No. 3, 1999, pp. 233-239.
[14]	F. J. Flores-Murrieta, G. Castañeda-Hernàndez, V. Granados-Soto and J. E. Herrera, “Increased Bioavailability of Sildenafil in Mexican Men,” JAMA, Vol. 283, No. 14, 2000, pp. 1825-1826. http://dx.doi.org/10.1001/jama.283.14.1825
[15]	S. C. Chien, Y. S. Uang, H. Y. Lin and K. Y. Hsu, “Pharmacokinetics of Nifedipine in Taiwanese,” Biopharmaceutics & Drug Disposition, Vol. 25, No. 2, 2004, pp. 77-84. http://dx.doi.org/10.1002/bdd.386