血管紧张素ⅱ的口服肾素抑制剂抑制人类的Aliskiren (SPP100):与卡托普利进行比较。
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Nussberger J, Wuerzner G,詹森C,作为人力资源
血管紧张素ⅱ的口服肾素抑制剂抑制人类的Aliskiren (SPP100):与卡托普利进行比较。
高血压。2002年1月,39 (1):E1-8。
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11799102 (在PubMed]
- 文摘
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肾素血管紧张素II (Ang)的主要决定因素是水平。因此,它总是出现希望降低Angⅱ水平通过直接抑制肾素。到目前为止,具体的肾素抑制剂缺乏力量和/或口头的可用性。我们测试了新的口服nonpeptidic肾素抑制剂SPP100(的octanamide Aliskiren 50%抑制浓度(IC50)低摩尔范围)在18个健康志愿者在100年一个常数更易使用双盲/ d钠饮食,我家的交换协议。在3期的8天,相隔6天的本事,每个志愿者收到2剂量水平的Aliskiren(低前高;40 - 80或160和640毫克/天)和随机安慰剂或20毫克卡托普利。Aliskiren耐受性良好。不出意料,这些血压正常的血压和心率保持不变。有剂量依赖性降低血浆肾素活性,和我,和二世后单剂量Aliskiren从40毫克。抑制仍明显和重要的重复剂量后最大Angⅱ水平减少89%和75%在天1和8日分别Aliskiren的最高剂量与安慰剂比较的时候。 At the same time, mean plasma active renin was increased 16- and 34-fold at the highest dose of Aliskiren. Plasma drug levels of Aliskiren were dose-dependent with maximal concentrations reached between 3 to 6 hours after administration; steady state was reached between 5 and 8 days after multiple dosing. Less than 1% of dose was excreted in the urine. Plasma and urinary aldosterone levels were decreased after doses of Aliskiren > or =80 mg and after enalapril. Aliskiren at 160 and 640 mg enhanced natriuresis on Day 1 by +45% and +62%, respectively, compared with placebo (100%, ie, 87+/-11 mmol/24h) and enalapril (+54%); kaliuresis remained unchanged. In conclusion, the renin inhibitor Aliskiren dose-dependently decreases Ang II levels in humans following oral administration. The effect is long-lasting and, at a dose of 160 mg, is equivalent to that of 20 mg enalapril. Aliskiren has the potential to become the first orally active renin inhibitor that provides a true alternative to ACE-inhibitors and Ang II receptor antagonists in therapy for hypertension and other cardiovascular and renal diseases.