Witte K, Weisser K, Neubeck M, Mutschler E, Lehmann K, Hopf R, Lemmer B
Zentrum der Pharmakologie, J.W. Goethe-Universität, Frankfurt/Main, Germany.
Clin Pharmacol Ther. 1993 Aug;54(2):177-86. doi: 10.1038/clpt.1993.129.
The cardiovascular effects and pharmacokinetics of once-daily enalapril were studied after single-dose and subchronic treatment in eight patients with hypertension by use of ambulatory blood pressure monitoring. Enalapril, 10 mg, was given at either 7 AM or 7 PM in a randomized crossover design. In addition, inhibition of serum converting enzyme was studied. Subchronic treatment at 7 AM significantly reduced blood pressure during the day but was less effective at night. Subchronic dosing at 7 PM significantly further decreased nighttime blood pressure followed by a slow increase during the day, with no effect on elevated afternoon values. Peak concentrations of enalaprilat were found 3.5 hours (morning) and 5.6 hours (evening) after drug intake (p < 0.05), whereas peak effects occurred 7.4 hours (morning) and 12 hours (evening) after drug administration. In conclusion, 24-hour blood pressure profiles in patients with hypertension were significantly influenced by the time of enalapril dosing. Differences in effect profiles could not be attributed to similar changes in pharmacokinetics or to different time courses of angiotensin converting enzyme inhibition.
采用动态血压监测，在8例高血压患者中进行单剂量和亚慢性治疗后，研究了每日一次依那普利的心血管效应和药代动力学。采用随机交叉设计，在上午7点或晚上7点给予10mg依那普利。此外，还研究了血清转化酶的抑制作用。上午7点进行亚慢性治疗可显著降低白天血压，但对夜间血压的效果较差。晚上7点进行亚慢性给药可显著进一步降低夜间血压，随后白天血压缓慢升高，对下午升高的值无影响。依那普利拉的峰值浓度在服药后3.5小时（上午）和5.6小时（晚上）出现（p<0.05），而峰值效应在给药后7.4小时（上午）和12小时（晚上）出现。总之，依那普利给药时间对高血压患者的24小时血压曲线有显著影响。效应曲线的差异不能归因于药代动力学的类似变化或血管紧张素转换酶抑制的不同时间进程。
