Onoyama K, Hirakata H, Tsuruda H, Ohchi N, Tomooka S, Motomura K, Omae T, Hayashi K, Fujishima M
Clin Pharmacol Ther. 1985 Oct;38(4):462-8. doi: 10.1038/clpt.1985.205.
The plasma concentration and urinary excretion of a newly developed angiotensin I converting enzyme inhibitor, alacepril (which is converted to captopril after absorption), were investigated in seven normal healthy subjects. Fifty milligrams of the drug was administered orally either in the fasting or in the fed state. In the fasting state, the time of maximal plasma concentration (tmax) was 1 hour for free captopril, 1.7 hours for protein-conjugated captopril, and 1.6 hours for total captopril. The biologic t1/2 of free, protein-conjugated, and total captopril was 1.9, 4.2, and 5 hours, respectively. In the fed state, neither tmax nor t1/2 changed, except that the tmax of free captopril was prolonged to 1.9 hours (P less than 0.01). Cumulative urinary excretion of free captopril at 8 hours was 35% of the drug administered in the fasting state and that of total captopril at 24 hours was 59%. These data did not differ significantly from those obtained after food intake. The biologic t1/2 of free captopril after alacepril dosing was longer than in previous studies of captopril per se. Because biologic or clinical effects have not been studied, it should be left conjectural whether alacepril is a longer-acting angiotensin I converting enzyme inhibitor. A prolonged effect of the drug can be expected by its administration after a meal.
在7名正常健康受试者中研究了一种新开发的血管紧张素I转换酶抑制剂阿拉普利（吸收后转化为卡托普利）的血浆浓度和尿排泄情况。该药物50毫克，分别在禁食或进食状态下口服。在禁食状态下，游离卡托普利的最大血浆浓度时间（tmax）为1小时，蛋白结合型卡托普利为1.7小时，总卡托普利为1.6小时。游离、蛋白结合型和总卡托普利的生物半衰期（t1/2）分别为1.9小时、4.2小时和5小时。在进食状态下，除游离卡托普利的tmax延长至1.9小时外（P<0.01），tmax和t1/2均未改变。禁食状态下给药后8小时游离卡托普利的累积尿排泄量为给药量的35%，24小时总卡托普利的累积尿排泄量为59%。这些数据与进食后获得的数据无显著差异。阿拉普利给药后游离卡托普利的生物半衰期比之前单独研究卡托普利时更长。由于尚未研究其生物学或临床效应，阿拉普利是否为长效血管紧张素I转换酶抑制剂仍有待推测。餐后给药有望使该药物产生延长的效应。
