Approaches to the rational choice of type 5 phosphodiesterase inhibitors in patients presenting with cardiovascular and endocrine diseases

Cover Page


After the advent of four type 5 phosphodiesterase inhibitors (PDEI 5), viz. sildenafil, tadalafil, vardenafil, and udenafil, designed for the treatment of erectile dysfunction both physicians and patients found themselves faced with the problem of choosing an optimal therapeutic option. This paper contains comparative data on the efficacy and safety of different PDEI 5. The approaches to the rational choice of these preparations for the treatment of patients presenting with cardiovascular and endocrine diseases are discussed. Comparative controlled clinical studies failed to yield definitive information about advantages of one or another agent representing this group of pharmaceutical products. Nevertheless, the currently available data permit to draw the conclusion that the use of vardenafil and tadalafil ensures better compliance of patients with the prescribed therapy. Certain authors advocate the desirability of vardenafil application to the treatment of patients presenting with a background pathology. It is emphasized that all available PDEI 5 have a beneficial safety profile, with wardenafil being virtually free from adverse side effects.

V V Rafal'skiĭ


A N Baglikov

  1. NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993;270:1:83-90.
  2. Johannes C.B., Araujo A.B., Feldman H.A. et al. Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study. J Urol 2000;163:2:460-463.
  3. Hakim L.S., Goldstein I. Diabetic sexual dysfunction. Endocrinol Metab Clin North Am 1996;25:2:379-400.
  4. Korenman S.G. New insights into erectile dysfunction: a practical approach. Am J Med 1998;105:2:135-144.
  5. Giugliano F., Maiorino M., Bellastella G. et al. Determinants of erectile dysfunction in type 2 diabetes. Int J Impot Res 2010;22:3:204-209.
  6. Mulhall J.P., Montorsi F. Evaluating preference trials of oral phosphodiesterase 5 inhibitors for erectile dysfunction. Eur Urol 2006;49:1:30-37.
  7. Blount M.A., Beasley A., Zoraghi R. et al. Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation. Mol Pharmacol 2004;66:1:144-152.
  8. Gbekor E., Bethell S., Fawcett L. et al. Phosphodiesterase 5 inhibitor profiles against all human phosphodiesterase families: implications for use as pharmacological tools. J Urol 2002;167:Suppl 246:967.
  9. Saenz de Tejada I., Angulo J., Cuevas P. et al. The phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil. Int J Impot Res 2001;13:5:282-290.
  10. Doh H., Shin C.Y., Son M. et al. Mechanism of erectogenic effect of the selective phosphodiesterase type 5 inhibitor, DA-8159. Arch Pharm Res 2002;25:6:873-878.
  11. Roehrborn C.G. Lower urinary tract symptoms, benign prostatic hyperplasia, erectile dysfunction, and phosphodiesterase-5 inhibitors. Rev Urol 2004;6:3:121-127.
  12. Teixeira C.E., Priviero F.B., Webb R.C. Differential effects of the phosphodiesterase type 5 inhibitors sildenafil, vardenafil, and tadalafil in rat aorta. J Pharmacol Exp Ther 2006;316:2:654-661.
  13. Kim T.E., Kim B.H., Kim J.R. et al. Effect of food on the pharmacokinetics of the oral phosphodiesterase 5 inhibitor udenafil for the treatment of erectile dysfunction. Br J Clin Pharmacol 2009;68:1:43-46.
  14. Gupta M., Kovar A., Meibohm B. The clinical pharmacokinetics of phosphodiesterase-5 inhibitors for erectile dysfunction. J Clin Pharmacol 2005;45:9:987-1003.
  15. Ku H.Y., Ahn H.J., Seo K.A. et al. The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dis 2008;36:6:986-990.
  16. Kim B.H., Lim H.S., Chung J.Y. et al. Safety, tolerability and pharmacokinetics of udenafil, a novel PDE-5 inhibitor, in healthy young Korean subjects. Br J Clin Pharmacol 2008;65:6:848-854.
  17. Auerbach S.M., Gittelman M., Mazzu A. et al. Simultaneous administration of vardenafil and tamsulosin does not induce clinically significant hypotension in patients with benign prostatic hyperplasia. Urology 2004;64:5:998-1004.
  18. Tatro D.S. Drug Interaction Facts. Wolter Kluwer Health Inc 2005.
  19. Guillaume M., Lonsdale F., Darstein C. et al. Hemodynamic interaction between a daily dosed phosphodiesterase 5 inhibitor, tadalafil, and the alpha-adrenergic blockers, doxazosin and tamsulosin, in middle-aged healthy male subjects. J Clin Pharmacol 2007;47:10:1303-1310.
  20. MacDiarmid S.A., Hill L.A., Volinn W., Hoel G. Lack of pharmacodynamic interaction of silodosin, a highly selective alpha1a-adrenoceptor antagonist, with the phosphodiesterase-5 inhibitors sildenafil and tadalafil in healthy men. Urology 2010;75:3:520-525.
  21. Jetter A., Kinzig-Schippers M., Walchner-Bonjean M. et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther 2002;71:1:21-29.
  22. Muirhead G.J., Faulkner S., Harness J.A., Taubel J. The effects of steady-state erythromycin and azithromycin on the pharmacokinetics of sildenafil in healthy volunteers. Br J Clin Pharmacol 2002;53:Suppl 1:37S-43S.
  23. Al-Ghazawi M.A., Tutunji M.S., AbuRuz S.M. The effects of pummelo juice on pharmacokinetics of sildenafil in healthy adult male Jordanian volunteers. Eur J Clin Pharmacol 2010;66:2:159-163.
  24. Muirhead G.J., Wulff M.B., Fielding A. et al. Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir. Br J Clin Pharmacol 2000;50:2:99-107.
  25. Sekar V., Lefebvre E., De Marez T. et al. Effect of repeated doses of darunavir plus low-dose ritonavir on the pharmacokinetics of sildenafil in healthy male subjects: phase I randomized, open-label, two-way crossover study. Clin Drug Inv 2008;28:8:479-485.
  26. Giuliano F., Jackson G., Montorsi F. et al. Safety of sildenafil citrate: review of 67 double-blind placebo-controlled trials and the postmarketing safety database. Int J Clin Pract 2010;64:2:240-255.
  27. Levitra(vardenafil), prescribing information. Bayer HealthCare Pharmaceuticals Inc., FDA 2008.
  28. Cialis (tadalafil), prescribing information. Eli Lilly and Company Indianapolis, FDA 2010.
  29. Viagra (sildenafil), prescribing information. Pfizer Labs Inc., FDA 2010.
  30. Rajagopalan P., Mazzu A., Xia C. et al. Effect of high-fat breakfast and moderate-fat evening meal on the pharmacokinetics of vardenafil, an oral phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction. J Clin Pharmacol 2003;43:3:260-267.
  31. Верткин А.Л. Выбор ингибитора фосфодиэстеразы типа 5: взгляд клинического фармаколога. Consilium Medicum 2004;6:502-506.
  32. Pfister O. et al. Cardiovascular disease and sexuality. Ther Umsch 2010;67:3:139-143.
  33. Sussman D.O. Pharmacokinetics, pharmacodynamics, and efficacy of phosphodiesterase type 5 inhibitors. J Am Osteopath Ass 2004;104:3:Suppl 4:S11-S15.
  34. Jackson G., Montorsi P., Cheitlin M.D. Cardiovascular safety of sildenafil citrate (Viagra): an updated perspective. Urology 2006;68:3:Suppl:47-60.
  35. Rohde G., Jorlaan P.J. Influence of vardenafil HCl on blood pressure and pharmacokinetics in hypertensive patients on nifedipine therapy. Pharacotherapy 2002;22:418.
  36. Ng C.F., Wong A., Cheng C.W. et al. Effect of vardenafil on blood pressure profile of patients with erectile dysfunction concomitantly treated with doxazosin gastrointestinal therapeutic system for benign prostatic hyperplasia. J Urol 2008;180:3:1042-1046.
  37. Carson C.C., Rajfer J., Eardley I. et al. The efficacy and safety of tadalafil: an update. BJU Int 2004;93:9:1276-1281.
  38. Fink H.A., Mac Donald R., Rutks I.R. et al. Sildenafil for male erectile dysfunction: a systematic review and meta-analysis. Arch Int Med 2002;162:12:1349-1360.
  39. Markou S., Perimenis P., Gyftopoulos K. et al. Vardenafil (Levitra) for erectile dysfunction: a systematic review and meta-analysis of clinical trial reports. Int J Impot Res 2004;16:6:470-478.
  40. Tsertsvadze A., Fink H.A., Yazdi F. et al. Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: a systematic review and meta-analysis. Ann Int Med 2009;151:9:650-661.
  41. Sommer F., Klotr T., Mathers M. et al. A comparative randomised multicentre study of the maximum dose of sildenafil, tadalafil and vardenafil. Eur Urol 2004;3:Suppl:105:409-410.
  42. von Keitz A., Rajfer J., Segal S. et al. A multicenter, randomized, double-blind, crossover study to evaluate patient preference between tadalafil and sildenafil. Eur Urol 2004;45:4:499-507; discussion 507-509.
  43. Eardley I., Mirone V., Montorsi F. et al. An open-label, multicentre, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in men naive to phosphodiesterase 5 inhibitor therapy. BJU Int 2005;96:9:1323-1332.
  44. Tolra J.R., Campana J.M., Ciutat L.F., Miranda E.F. Prospective, randomized, open-label, fixed-dose, crossover study to establish preference of patients with erectile dysfunction after taking the three PDE-5 inhibitors. J Sex Med 2006;3:5:901-909.
  45. Rubio-Aurioles E., Porst H., Eardley I., Goldstein I. Comparing vardenafil and sildenafil in the treatment of men with erectile dysfunction and risk factors for cardiovascular disease: a randomized, double-blind, pooled crossover study. J Sex Med 2006;3:6:1037-1049.
  46. Toshiyasu A., Tetsuya I., Katsurou T. et al. Comparative study for the treatment of erectile dysfunction with sildenafil and vardenafil-multi-centric research in Nagano City. Nippon Hinyokika Gakkai Zasshi 2009;100:1:1-6.
  47. Carson C.C., Hatzichristou D.G., Carrier S. et al. Erectile response with vardenafil in vardenafil nonresponders: a multicentre, double-blind, 12-week, flexible-dose, placebo-controlled erectile dysfunction clinical trial. BJU Int 2004;94:9:1301-1309.
  48. Hatzichristou D.G., Aliotta P., Auerbach S. et al. Erectile response to vardenafil in men with a history of nonresponse to sildenafil: a time-from-dosing descriptive analysis. Clin Ther 2005;27:9:1452-1461.
  49. Stroberg P., Murphy A., Costigan T. Switching patients with erectile dysfunction from sildenafil citrate to tadalafil: results of a European multicenter, open-label study of patient preference. Clin Ther 2003;25:11:2724-2737.
  50. Ozgur B.C., Gonenc F., Yazicioglu A.H. Sildenafil or vardenafil nonresponders' erectile response to tadalafil. Urol J 2009;6:4:267-271.
  51. Paick J.S., Kim S.W., Yang D.Y. et al. The efficacy and safety of udenafil, a new selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction. J Sex Med 2008;5:946-953.
  52. Paick J.S., Kim S.W., Park Y.K. et al. The efficacy and safety of udenafil [Zydena] for the treatment of erectile dysfunction in hypertensive men taking concomitant antihypertensive agents. J Sex Med 2009;6:3166-3176.
  53. Taylor J., Baldo O.B., Storey A. et al. Differences in side-effect duration and related bother levels between phosphodiesterase type 5 inhibitors. BJU Int 2009;103:10:1392-1395.
  54. Hellstrom W.J., Gittelman M., Jarow J. et al. An evaluation of semen characteristics in men 45 years of age or older after daily dosing with tadalafil 20mg: results of a multicenter, randomized, double-blind, placebo-controlled, 9-month study. Eur Urol 2008;53:5:1058-1065.
  55. Pomara G., Morelli G., Canale D. et al. Alterations in sperm motility after acute oral administration of sildenafil or tadalafil in young, infertile men. Fertil Steril 2007;88:4:860-865.
  56. Jarvi K., Dula E., Drehobl M. et al. Daily vardenafil for 6 months has no detrimental effects on semen characteristics or reproductive hormones in men with normal baseline levels. J Urol 2008;179:3:1060-1065.
  57. Pickering T.G., Shepherd A.M., Puddey I. et al. Sildenafil citrate for erectile dysfunction in men receiving multiple antihypertensive agents: a randomized controlled trial. Am J Hypertens 2004;17:12:Pt 1:1135-1142.
  58. van Ahlen H., Wahle K., Kupper W. et al. Safety and efficacy of vardenafil, a selective phosphodiesterase 5 inhibitor, in patients with erectile dysfunction and arterial hypertension treated with multiple antihypertensives. J Sex Med 2005;2:6:856-864.
  59. Valiquette L., Montorsi F., Auerbach S. Vardenafil demonstrates first-dose success and reliability of penetration and maintenance of erection in men with erectile dysfunction - RELY-II. Can Urol Ass J 2008;2:3:187-195.
  60. Shabsigh R., Duval S., Shah M. et al. Efficacy of vardenafil for the treatment of erectile dysfunction in men with hypertension: a meta-analysis of clinical trial data. Curr Med Res Opin 2007;23:10:2453-2460.
  61. Lewis R.W., Sadovsky R., Eardley I. et al. The efficacy of tadalafil in clinical populations. J Sex Med 2005;2:4:517-531.
  62. Blonde L. Sildenafil citrate for erectile dysfunction in men with diabetes and cardiovascular risk factors: a retrospective analysis of pooled data from placebo-controlled trials. Curr Med Res Opin 2006;22:11:2111-2120.
  63. Mazo E.B., Gamidov S.I., Iremashvili V.V., Gasanov R.V. Efficacy of phosphodiesterase inhibitors in the treatment of patients with organic erectile dysfunction: a comparative study. Urologiia 2009;1:40, 43-46.


Abstract - 1618




Copyright (c) 2010 Rafal'skiĭ V.V., Baglikov A.N.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies