Jackson B, Johnston C I
Clin Exp Pharmacol Physiol. 1984 Jul-Aug;11(4):355-9. doi: 10.1111/j.1440-1681.1984.tb00278.x.
The acute and chronic effects of enalapril (MK421) were assessed in a double-blind randomized trial in subjects with essential hypertension. In acute studies, twelve subjects received enalapril (10 mg p.o.), following which there was a fall in blood pressure, maximal at 6 h and lasting for 24 h. Serum MK422 (enalaprilic acid, the bioactive form of enalapril) and serum angiotensin converting enzyme (ACE) inhibition had a similar time course with good correlation between drug levels and ACE inhibition (P less than 0.001, r = 0.98, n = 16) and between ACE inhibition and the hypotensive effect (P less than 0.001, r = 0.84, n = 16). In chronic studies enalapril was titrated from 5 mg to 20 mg twice a day in eleven hypertensive patients to achieve a diastolic blood pressure less than 90 mmHg. Treatment continued for 3-12 months. Increasing serum MK422 was correlated with reducing serum ACE activity (P less than 0.001, r = 0.8, n = 104). The fall in blood pressure correlated both with serum MK422 level (P less than 0.05, r = 0.37, n = 39) as well as ACE inhibition (P less than 0.01, r = 0.45, n = 42). The drug level:ACE inhibition curve was shifted to the right during chronic enalapril treatment. ID50 for serum ACE was 32 ng MK422/ml following the single 10 mg dose of MK421 and 70 ng MK422/ml during chronic treatment. Blood pressure falls during acute and chronic treatment were similar over the range of serum MK422 levels achieved. The shift in the drug level:ACE inhibition curve suggests induction of ACE during chronic treatment with enalapril in man.
在一项针对原发性高血压患者的双盲随机试验中评估了依那普利（MK421）的急性和慢性效应。在急性研究中，12名受试者口服依那普利（10毫克），随后血压下降，6小时时降至最大幅度，并持续24小时。血清MK422（依那普利酸，依那普利的生物活性形式）和血清血管紧张素转换酶（ACE）抑制作用具有相似的时间进程，药物水平与ACE抑制作用之间具有良好的相关性（P小于0.001，r = 0.98，n = 16），ACE抑制作用与降压效果之间也具有良好的相关性（P小于0.001，r = 0.84，n = 16）。在慢性研究中，11名高血压患者将依那普利剂量从每天5毫克滴定至20毫克，分两次服用，以使舒张压低于90毫米汞柱。治疗持续3至12个月。血清MK422升高与血清ACE活性降低相关（P小于0.001，r = 0.8，n = 104）。血压下降与血清MK422水平相关（P小于0.05，r = 0.37，n = 39），也与ACE抑制作用相关（P小于0.01，r = 0.45，n = 42）。在依那普利慢性治疗期间，药物水平：ACE抑制曲线向右移动。单次服用10毫克MK421后血清ACE的ID50为32纳克MK422/毫升，慢性治疗期间为70纳克MK422/毫升。在达到的血清MK422水平范围内，急性和慢性治疗期间的血压下降相似。药物水平：ACE抑制曲线的移动表明在人体依那普利慢性治疗期间ACE被诱导。
