Ferguson R K, Vlasses P H, Swanson B N, Mojaverian P, Hichens M, Irvin J D, Huber P B
Clin Pharmacol Ther. 1982 Jul;32(1):48-53. doi: 10.1038/clpt.1982.125.
The new angiotensin converting enzyme inhibitor enalapril maleate was given in single oral doses of 2.5, 5, and 10 mg to 11 hospitalized patients with uncomplicated essential hypertension who were on a 150-mEq sodium diet. All doses of enalapril induced reduction of mean seated diastolic blood pressure (SDBP). The magnitude of the initial SDBP reduction was not dose related, but the duration of effect was longer (greater than 12 hr) after the 5 and 10 mg. After dosing, mean plasma angiotensin converting enzyme activity (ACE) and aldosterone concentration (PAC) fell, while plasma renin activity (PRA) rose. Serum concentrations of the active diacid from of enalapril increased linearly with dosage; ACE was inhibited maximally at concentrations above 10 ng/ml. During repeated dosing in the outpatient trial there was attenuation of the antihypertensive effect (12 to 24 hr after dosing) in eight of 10 patients. Despite dose increases only two patients achieved SDBP control (less than or equal to 90 mm Hg). In the five patients in whom 50 mg/day hydrochlorothiazide was added near the end of the trail mean SDBP was further reduced. Enalapril was well tolerated. Further studies of the drug, especially in combination with diuretic, are needed.
对11例住院的单纯原发性高血压患者给予单剂量口服2.5、5和10mg的新型血管紧张素转换酶抑制剂马来酸依那普利，这些患者均采用150mEq钠饮食。所有剂量的依那普利均能使平均坐位舒张压（SDBP）降低。初始SDBP降低的幅度与剂量无关，但5mg和10mg剂量后的作用持续时间更长（大于12小时）。给药后，平均血浆血管紧张素转换酶活性（ACE）和醛固酮浓度（PAC）下降，而血浆肾素活性（PRA）升高。依那普利活性二酸形式的血清浓度随剂量呈线性增加；在浓度高于10ng/ml时，ACE受到最大程度的抑制。在门诊试验的重复给药过程中，10例患者中有8例出现降压作用减弱（给药后12至24小时）。尽管增加了剂量，但只有2例患者的SDBP得到控制（小于或等于90mmHg）。在试验接近尾声时，对5例患者加用了每日50mg氢氯噻嗪，平均SDBP进一步降低。依那普利耐受性良好。需要对该药物进行进一步研究，尤其是与利尿剂联合使用的研究。
