Schäfers R F, Fokuhl B, Wasmuth A, Schumacher H, Taguchi K, de Mey C, Philipp T, Michel M C
Department of Medicine, University of Essen, Germany.
Br J Clin Pharmacol. 1999 Jan;47(1):67-74. doi: 10.1046/j.1365-2125.1999.00856.x.
In patients with lower urinary tract symptoms suggestive of benign prostatic obstruction the alpha1-adrenoceptor antagonist terazosin lowers blood pressure whereas only very small if any alterations were reported with the alpha1-adrenoceptor antagonist tamsulosin. Therefore, we have compared the vascular alpha1-adrenoceptor antagonism of tamsulosin and terazosin directly.
Ten healthy subjects were investigated in a randomized, single-blind, three-way cross-over design and received a single dose of 0.4 mg tamsulosin, 5 mg terazosin or placebo on 3 study days at least 1 week apart. Before and 1, 3, 5, 7, 10 and 23.5 h after drug intake, alterations of diastolic blood pressure and other haemodynamic parameters in response to a graded infusion of the alpha1-adrenoceptor agonist phenylephrine were determined non-invasively.
At most time points tamsulosin inhibited phenylephrine-induced diastolic blood pressure elevations significantly less than terazosin (5 h time point: median difference in inhibition 35%, 95% CI: 18.7-50.3%). On the other hand, phenylephrine-induced changes of cardiac output, heart rate and stroke volume were similar during both active treatments.
In doses equi-effective for treatment of lower urinary tract symptoms tamsulosin causes less inhibition of vasoconstriction than terazosin.
在有提示良性前列腺梗阻的下尿路症状患者中,α1肾上腺素能受体拮抗剂特拉唑嗪可降低血压,而α1肾上腺素能受体拮抗剂坦索罗辛即使有改变也非常小。因此,我们直接比较了坦索罗辛和特拉唑嗪对血管α1肾上腺素能受体的拮抗作用。
采用随机、单盲、三交叉设计对10名健康受试者进行研究,在至少间隔1周的3个研究日分别给予单剂量0.4mg坦索罗辛、5mg特拉唑嗪或安慰剂。在服药前及服药后1、3、5、7、10和23.5小时,通过无创方式测定对α1肾上腺素能受体激动剂去氧肾上腺素进行分级输注时舒张压和其他血流动力学参数的变化。
在大多数时间点,坦索罗辛对去氧肾上腺素诱导的舒张压升高的抑制作用明显小于特拉唑嗪(5小时时间点:抑制作用的中位数差异为35%,95%CI:18.7-50.3%)。另一方面,在两种活性治疗期间,去氧肾上腺素诱导的心输出量、心率和每搏量变化相似。
在治疗下尿路症状等效剂量下,坦索罗辛对血管收缩的抑制作用小于特拉唑嗪。