Jacot des Combes B, Turini G A, Brunner H R, Porchet M, Chen D S, Sen S
J Cardiovasc Pharmacol. 1983 Jul-Aug;5(4):511-6.
The new converting enzyme inhibitor CGS 13945 was evaluated in 14 male volunteers. The study consisted of two parts. First, the capacity of a single oral dose (10, 20, 50, 100, 250, or 500 mg) to inhibit the pressor response to exogenous angiotensin I was tested, with blood pressure and heart rate monitored continuously through an intra-arterial catheter. The 250-mg and particularly the 500-mg dose markedly reduced the pressor response to angiotensin I within 1/2 h and for a period exceeding 4 h. There was a close correlation between the pressor response to angiotensin I and plasma converting enzyme activity. In a second part, plasma renin and converting enzyme activity, angiotensin I and II, and plasma aldosterone were measured serially before and up to 48 h after oral administration of either 250 or 500 mg of CGS 13945 to six volunteers each. As expected, plasma renin activity and angiotensin I levels rose, while plasma converting enzyme activity and angiotensin II and aldosterone levels fell within 1/2 h. Twenty-four hours following administration of 500 mg CGS 13945, plasma converting enzyme had not quite returned to base line. No side effects were observed. CGS 13945 seems less potent than previously studied converting enzyme inhibitors, but equally effective and relatively long acting.
新型转化酶抑制剂CGS 13945在14名男性志愿者身上进行了评估。该研究包括两个部分。首先，测试单次口服剂量（10、20、50、100、250或500毫克）抑制对外源性血管紧张素I升压反应的能力，通过动脉内导管持续监测血压和心率。250毫克剂量，尤其是500毫克剂量在半小时内显著降低了对血管紧张素I的升压反应，且作用持续超过4小时。对血管紧张素I的升压反应与血浆转化酶活性之间存在密切相关性。在第二部分中，对6名志愿者分别口服250毫克或500毫克CGS 13945，在服药前及服药后长达48小时内连续测量血浆肾素和转化酶活性、血管紧张素I和II以及血浆醛固酮。正如预期的那样，血浆肾素活性和血管紧张素I水平升高，而血浆转化酶活性以及血管紧张素II和醛固酮水平在半小时内下降。服用500毫克CGS 13945后24小时，血浆转化酶尚未完全恢复至基线水平。未观察到副作用。CGS 13945似乎比之前研究的转化酶抑制剂效力稍低，但效果相当且作用时间相对较长。
