Oger S, Behr-Roussel D, Gorny D, Lebret T, Denoux Y, Alexandre L, Giuliano F
Combination of Alfuzosin and Tadalafil Exerts an Additive Relaxant Effect on Human Detrusor and Prostatic Tissues In Vitro. [JOURNAL ARTICLE]
Eur Urol 2009 May 3.
BACKGROUND: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are highly prevalent in aging men and are strongly linked. Alpha(1)-blockers such as alfuzosin are effective monotherapies for LUTS. Phosphodiesterase type 5 (PDE5) inhibitors such as tadalafil are the first-line treatment for ED. Both drugs act by two different mechanisms of action on common urogenital target organs and, thus, may have additive effects.
OBJECTIVES: We evaluated in vitro the effects of alfuzosin, tadalafil, and the combination of both on human detrusor and prostatic smooth muscle.
DESIGN, SETTING, AND PARTICIPANTS: Prostatic and bladder tissue were obtained from patients (n=20 and n=17, respectively) undergoing cystoprostatectomy for bladder cancer.
MEASUREMENTS: In organ baths, isolated prostatic strips and isolated bladder strips were incubated with vehicle, tadalafil (10(-6) M and 10(-5) M), alfuzosin (3x10(-8) M or 10(-6) M and 10(-5) M) or a combination. Concentration-response curves (CRCs) to norepinephrine were generated on prostatic strips and detrusor strips precontracted with carbachol. Strips were also submitted to electrical field stimulation (EFS).
RESULTS AND
LIMITATIONS: When alfuzosin and tadalafil were combined, the maximal relaxation to norepinephrine on carbachol-precontracted detrusor strips was significantly increased compared with tadalafil alone, and EFS-induced detrusor contractions were better inhibited compared with each compound alone. Tadalafil significantly inhibited norepinephrine-induced prostatic strip contractions by reducing the maximal effect, whereas alfuzosin shifted the CRC of norepinephrine to the right. Combining both tadalafil and alfuzosin resulted in a greater relaxant effect. Likewise, the combination was more effective at reducing EFS-induced contractions compared with each compound alone.
CONCLUSIONS: The combination of alfuzosin and tadalafil exerts an additive effect of inhibiting adrenergic smooth muscle tone of prostatic tissue and EFS-induced detrusor contractions and conversely, of enhancing adrenergic relaxation of detrusor precontracted with carbachol. These experiments provide experimental support for the clinical investigation of the combination of alpha1-blockers and PDE5 inhibitors in the treatment of LUTS.
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