Witte P U, Irmisch R, Hajdú P, Metzger H
Eur J Clin Pharmacol. 1984;27(5):577-81. doi: 10.1007/BF00556895.
The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme inhibitor HOE 498 were investigated in 10 healthy normotensive male subjects. Serum levels of the active metabolite M 1 (dicarboxylic acid) of HOE 498 were measured by HPLC up to 14 days after a single oral dose of 10 mg HOE 498. Peak serum concentration of M 1 between 5-50 ng/ml was observed 1.5-3.0 h after administration. The serum concentration-time curve of M 1 was polyphasic and exhibited a prolonged terminal phase with a half-life of approximately 110 h. Despite the long terminal half-life M 1 could not be detected in urine later than 72 h after administration. The activity of the angiotensin converting enzyme in plasma was completely suppressed for up to 12 h, and 72 h after dosing 50% inhibition of the enzyme was still observed.
在10名健康的血压正常男性受试者中研究了血管紧张素转换酶抑制剂HOE 498的药代动力学和药效学。单次口服10 mg HOE 498后，通过高效液相色谱法测定HOE 498活性代谢物M1（二羧酸）的血清水平，长达14天。给药后1.5 - 3.0小时观察到M1的血清峰值浓度在5 - 50 ng/ml之间。M1的血清浓度-时间曲线呈多相，终末相延长，半衰期约为110小时。尽管终末半衰期长，但给药后72小时后在尿液中未检测到M1。血浆中血管紧张素转换酶的活性被完全抑制长达12小时，给药72小时后仍观察到该酶50%的抑制率。
