UroToday.com – This updated review of tadalafil (Cialis), one of the three available phosphodiesterase type 5 (PDE5) inhibitors that revolutionized the treatment of erectile dysfunction (ED), analyzes its latest clinical studies. Tadalafil’s most unique and identifying characteristic is its long half-life of 17.5 hours, compared with 4 hours for sildenafil (Viagra) and vardenafil (Levitra).
We have known since 2003 that this longer half-life provides a therapeutic window of 36 hours.1 Recently, studies have shown that tadalafil’s longer half-life lends itself to once-daily dosing as well. 2-7 Steady-state plasma concentrations are attained within five days of initiating daily dosing. 8 Based on its pharmacokinetics, after five days of once-daily dosing, the plasma concentration of tadalafil achieved with a 2.5 mg and 5 mg daily dose is 4 mg and 8 mg, respectively.
The FDA announced approval for once-daily dosing of tadalafil in January 2008, adding an option in the clinician’s armamentarium against ED that unlinks the temporal association between a medication and the sexual encounter.
The new dosing schedule of tadalafil prompted us to write this updated review of its use in the treatment of ED. In the review we also briefly discuss ED, the physiology of penile erection, and the role of PDE5, before focusing exclusively on tadalafil and comparing it with its PDE5 inhibitor counterparts.
In addition to its latest clinical studies, the review includes the historical development of tadalafil as a PDE5 inhibitor first called IC351 in 1993 that was initially tested as a cardiovascular drug, as well as a comprehensive report of its pharmacology. The studies highlighted in the review include tadalafil in the general ED population, difficult-to-treat ED, ED secondary to diabetes mellitus, and ED after prostate cancer treatment.
Tadalafil is a safe, well-tolerated, and efficacious treatment for all severities and etiologies of ED, and its half-life of 17.5 hours lends itself to a longer therapeutic window with on-demand dosing and effective steady-state plasma concentrations with once-daily dosing.
1. Porst H, Padma-Nathan H, Giuliano F, et al. 2003. Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Urology, 62:121-5.
2. McMahon C. 2004. Efficacy and safety of daily tadalafil in men with erectile dysfunction previously unresponsive to on-demand tadalafil. J Sex Med, 1:292-300.
3. McMahon C. 2005. Comparison of efficacy, safety, and tolerability of on-demand tadalafil and daily dosed tadalafil for the treatment of erectile dysfunction. J Sex Med, 2:415-25.
4. Porst H, Giuliano F, Glina S, et al. 2006. Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5 mg and 10 mg in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial. Eur Urol, 50:351-9.
5. Rajfer J, Aliotta PJ, Steidle CP, et al. 2007. Tadalafil dosed once a day in men with erectile dysfunction: a randomized, double-blind, placebo-controlled study in the US. Int J Impot Res, 19:95-103.
6. Hatzichristou D, Gambla M, Rubio-Aurioles E, et al. 2008. Efficacy of tadalafil once daily in men with diabetes mellitus and erectile dysfunction. Diabet Med, 25:138-46.
7. Porst H, Rajfer J, Casabé A, et al. 2008. Long-term safety and efficacy of tadalafil 5 mg dosed once daily in men with erectile dysfunction. J Sex Med, Sep;5(9):2160-9.
8. Forgue ST, Patterson BE, Bedding AW, et al. 2006. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol, 61:280-8.
Written by Robert M Coward, MD and Culley C Carson III, MD as part of Beyond the Abstract on UroToday.com.
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