Lenfant B, Mouren M, Bryce T, De Lauture D, Strauch G
Roussel UCLAF, Romainville, France.
J Cardiovasc Pharmacol. 1994;23 Suppl 4:S38-43.
The pharmacokinetics and dose proportionality of trandolapril, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated in 12 healthy male volunteers in a four-way randomized crossover study over the therapeutic dose range, 0.5-4 mg. Trandolapril is rapidly absorbed, with a single elimination half-life (t1/2) of 0.72 h, irrespective of dose. Peak plasma levels (Cmax) occurred at 0.5 h and were proportional to the dose, as was the area under the plasma concentration-time curve (AUC). Concentration of the active metabolite (trandolaprilat) increased with increasing doses but in a nonlinear fashion, probably owing to saturable plasma ACE binding. However, the Cmax and AUC values for trandolaprilat were directly proportional to the highest doses, 2 and 4 mg, suggesting linear kinetics for the trandolaprilat, which is not bound to ACE. Trandolapril showed linear kinetics but trandolaprilat showed some features of nonlinear kinetics, particularly at low doses.
在一项针对12名健康男性志愿者的四向随机交叉研究中，在0.5 - 4毫克的治疗剂量范围内，对新型血管紧张素转换酶（ACE）抑制剂群多普利的药代动力学和剂量比例关系进行了研究。群多普利吸收迅速，无论剂量如何，其单次消除半衰期（t1/2）均为0.72小时。血浆峰值水平（Cmax）在0.5小时出现，且与剂量成正比，血浆浓度-时间曲线下面积（AUC）也是如此。活性代谢物（群多普利拉）的浓度随剂量增加而升高，但呈非线性方式，这可能是由于血浆ACE结合饱和所致。然而，群多普利拉的Cmax和AUC值与最高剂量2毫克和4毫克直接成正比，这表明未与ACE结合的群多普利拉具有线性动力学。群多普利表现出线性动力学，但群多普利拉表现出一些非线性动力学特征，尤其是在低剂量时。
