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BASIC
AND TRANSLATIONAL UROLOGY
Combination
of alfuzosin and tadalafil exerts an additive relaxant effect on human
detrusor and prostatic tissues in vitro
Oger S, Behr-Roussel D, Gorny D, Lebret T, Denoux Y, Alexandre L, Giuliano F
Pelvipharm, Orsay Parc, Orsay, France
Eur Urol. 2009 May 3. [Epub ahead of print]
- 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.
- Editorial Comment
Prescription of an association of alpha-blockers and PDE-5 inhibitors has been
increasingly in clinical practice, since lower urinary tract symptoms (LUTS)
and erectile dysfunction (ED) are commonly associated. Also, it has been
demonstrated a positive effect of PDE-5 in LUTS. On the other hand, it has
been demonstrated that LUTS would predispose to sexual dysfunction. Therefore,
an emerging concept is that the combination of an alpha-blocker and a PDE-5
inhibitor is the most effective therapy to treat LUTS secondary to BPH. The
present study demonstrated in vitro that the combination of alfuzosin and
tadalafil shows an additive relaxant effect on human prostate and detrusor
tissue, and therefore, the association could be more effective than monotherapy
in relieving LUTS associated with BPH.
Dr. Francisco J. B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, RJ, Brazil
E-mail: sampaio@urogenitalresearch.org
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