Clinical Experience in Europe with Uroselective &amp;alpha;&lt;sub&gt;1&lt;/sub&gt;-Antagonists

Debruyne, F.M.J.; Poel, H.G. Van Der

doi:10.1159/000052319

Cited by 17 publications

(15 citation statements)

References 34 publications

(24 reference statements)

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“…However, these have been observed in therapeutic doses rarely [22,23]. The other important side effect of a blockers is impaired ejaculation or retrograde ejaculation.…”

Section: Discussionmentioning

confidence: 99%

Terazosin in the Treatment of Premature Ejaculation: A Short-term Follow-up

et al. 2005

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“…However, these have been observed in therapeutic doses rarely [22,23]. The other important side effect of a blockers is impaired ejaculation or retrograde ejaculation.…”

Section: Discussionmentioning

confidence: 99%

Terazosin in the Treatment of Premature Ejaculation: A Short-term Follow-up

et al. 2005

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“…Indeed, the relative contribution of specific subtypes to efficacy and safety remains unclear (Hieble and Ruffolo, 1997;de May, 1999;Lowe, 1999). Therefore, controlled head-to-head comparative clinical studies with existing as well as new ␣ 1 -adrenoceptor antagonists with unique subtype selectivity profiles will be needed to prove or disprove this hypothesis (Debruyne and Van der Poel, 1999). Nevertheless, the findings for tamsulosin in this study validate the utility of the conscious dog model as a tool for measuring and perhaps predicting uroselectivity and efficacy of novel ␣ 1a -/␣ 1d -selective adrenoceptor antagonists such as fiduxosin in human.…”

Section: Discussionmentioning

confidence: 99%

Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α₁-Adrenoceptor Antagonists

Witte¹,

Brune²,

Katwala³

et al. 2002

J Pharmacol Exp Ther

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Fiduxosin is a new ␣ 1 -adrenoceptor antagonist targeted for the treatment of symptomatic benign prostatic hyperplasia. The purpose of this study was to determine and compare the potencies of the ␣ 1 -adrenoceptor antagonists terazosin, doxazosin, tamsulosin, and fiduxosin, based on relationships between plasma drug concentrations and blockade of phenylephrine (PE)-induced intraurethral (IUP) and mean arterial pressure (MAP) responses after single oral dosing in conscious male beagle dogs. Magnitude of blockade and plasma concentrations were evaluated at selected time points over 24 h. All drugs produced dose-dependent antagonism of PE-induced IUP and MAP responses. When IUP and MAP blockade effects were plotted against drug plasma concentrations, direct relationships were observed that were well described by the sigmoidal maximal effect model. IUP IC 50 values for terazosin, doxazosin, tamsulosin, and fiduxosin were 48.6, 48.7, 0.42, and 261 ng/ml, respectively. MAP IC 50 values were 12.2, 13.8, 1.07, and 1904 ng/ml, respectively. Uroselectivity index values, defined as MAP IC 50 /IUP IC 50 , were 0.25, 0.28, 2.6, and 7.3, respectively. These results extend previous observations with terazosin in this model, showing that doxazosin exhibits a uroselectivity index comparable to terazosin, consistent with the lack of ␣ 1 -adrenoceptor subtype selectivity or uroselectivity of these drugs. Tamsulosin, an ␣ 1a -/␣ 1d -subtype selective agent, had an index value approximately 10-fold greater than the nonselective drugs. Based on its pharmacokinetic profile and a relative uroselectivity 29-fold greater than the nonselective drugs, fiduxosin is expected to exhibit greater selectivity for urethral compared with vascular ␣ 1 -adrenoceptors in human and should be a novel, long-acting, uroselective ␣ 1 -adrenoceptor antagonist.␣ 1 -Adrenoceptor antagonists represent first-line therapy for the pharmacological treatment of benign prostatic hyperplasia (BPH), in part by relaxing prostatic smooth muscle (Lowe, 1999). Fiduxosin (ABT-980) is a novel ␣ 1 -adrenoceptor antagonist. Compared with other clinical agents, such as terazosin, doxazosin, and tamsulosin, fiduxosin exhibits a somewhat different ␣ 1 -adrenoceptor subtype selectivity profile. Radioligand binding potencies at human ␣ 1a -, ␣ 1b -, and ␣ 1d -adrenoceptors are reported to be 1.81, 1.16, and 0.67 nM for terazosin; 0.79, 0.80, and 0.81 nM for doxazosin; 0.03, 0.60, and 0.06 nM for tamsulosin; and 0.16, 24.89, and 0.92 nM for fiduxosin, respectively (Hancock et al., 1998b(Hancock et al., , 2002, showing fiduxosin to be selective for ␣ 1a -and ␣ 1d -adrenoceptors compared with ␣ 1b -adrenoceptors to a greater extent than tamsulosin.Accumulating data suggest that extraprostatic ␣ 1 -adrenoceptors in bladder, spinal cord, ganglia, or nerve terminals may also contribute to ameliorating the irritative and voiding symptoms of BPH (Fitzpatrick, 2000;Schwinn and Michelotti, 2000). Three subtypes of ␣ 1 -adrenoceptors are known to exist, ␣ 1A -, ␣ 1B -, and ␣ 1D -adr...

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“…The treatment of patients with symptomatic BPH using alfuzosin is well established and its effect on LUTS well characterized. Alfuzosin is a selective a 1 -adrenoceptor antagonist with con®rmed ef®cacy and good cardiovascular tolerance in the treatment of BPO [10,11,19]. Besides improving LUTS, treatment with alfuzosin improves the quality of life of patients with BPO [21,22,28].…”

Section: Discussionmentioning

confidence: 99%

“…One common option for the medical management of BPH is treatment with a 1 -blockers, e.g. sustained-release (SR) alfuzosin [10]. Alfuzosin acts on the dynamic component of BPO by decreasing the sympathetically controlled tone of prostatic smooth muscle [9,11,12].…”

Section: Introductionmentioning

confidence: 99%

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The clinical uroselectivity of alfuzosin is not significantly affected by the age of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

et al. 2000

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The clinical uroselectivity of alfuzosin is not signi®cantly affected by the age of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia i.e. <56, 56±65, 66±75 and >75 years. All groups of patients showed a mean IPSS decrease of 11±12 (55.8±65.4% from baseline) at the end of the study, while the QoL decreased by 2±3 points (55.6±63.6% from baseline). There were no relevant effects of age on the ef®cacy of the treatment. Moreover, alfuzosin was well tolerated independently of the age of the patient; 1.2% of the patients enrolled withdrew because of adverse events. The qualitative distribution of vasodilatory/nonvasodilatory adverse events was similar in all age groups. The incidence of asymptomatic orthostatic hypotension was low (0.58%) and not affected by the age of the patients. Conclusion This study con®rms that the clinical uroselectivity of SR-alfuzosin, already described in randomized controlled studies, is not signi®cantly affected in clinical practice by the age of the patients. This is considered particularly relevant to the characteristics of patients with BPH, as they are mostly elderly men.

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Clinical Experience in Europe with Uroselective α<sub>1</sub>-Antagonists

Cited by 17 publications

References 34 publications

Terazosin in the Treatment of Premature Ejaculation: A Short-term Follow-up

Terazosin in the Treatment of Premature Ejaculation: A Short-term Follow-up

Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α₁-Adrenoceptor Antagonists

The clinical uroselectivity of alfuzosin is not significantly affected by the age of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

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Clinical Experience in Europe with Uroselective &alpha;<sub>1</sub>-Antagonists

Cited by 17 publications

References 34 publications

Terazosin in the Treatment of Premature Ejaculation: A Short-term Follow-up

Terazosin in the Treatment of Premature Ejaculation: A Short-term Follow-up

Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α1-Adrenoceptor Antagonists

The clinical uroselectivity of alfuzosin is not significantly affected by the age of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

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Clinical Experience in Europe with Uroselective α<sub>1</sub>-Antagonists

Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α₁-Adrenoceptor Antagonists