Eckert M, Pozenel H, Pillat B
J Clin Pharmacol. 1984 Apr;24(4):165-73. doi: 10.1002/j.1552-4604.1984.tb01826.x.
The pharmacokinetic behavior and hemodynamic effects of tiapamil, a calcium antagonist, were studied in 16 cardiac patients during an eight-day treatment course, giving oral doses of 600 mg daily. The hemodynamic effects were investigated using exercise performance tests, thallium stress scintigraphy, and radionuclide ventriculography. The areas under the plasma concentration-time curve after the final dose were greater than after the first dose for both tiapamil (+53 per cent) and its metabolite (+24 per cent). One possible explanation is that tiapamil undergoes saturable intestinal wall metabolism. Alternatively, like verapamil, it may undergo a saturable hepatic elimination process. The hemodynamic test series showed that, despite increasing the exercise tolerance, tiapamil significantly reduced the rate-pressure product, an index of myocardial oxygen requirement. Regional myocardial perfusion clearly improved. Ventriculography showed a significant increase in ejection fraction (+18 per cent), cardiac index (+12 per cent), and stroke volume index (+19 per cent). At the same time, the measured mean arterial pressure decreased significantly by about 10 per cent and the calculated peripheral vascular resistance, by about 19 per cent.
在一个为期八天的治疗过程中，对16名心脏病患者进行了研究，每日口服600毫克钙拮抗剂替帕米，以观察其药代动力学行为和血流动力学效应。采用运动性能测试、铊应激闪烁扫描和放射性核素心室造影来研究血流动力学效应。最终剂量后替帕米及其代谢物的血浆浓度-时间曲线下面积均大于首次剂量后（替帕米增加53%，代谢物增加24%）。一种可能的解释是替帕米经历了饱和性肠壁代谢。或者，与维拉帕米一样，它可能经历了饱和性肝脏消除过程。血流动力学测试系列表明，尽管替帕米提高了运动耐量，但它显著降低了心肌需氧量指标心率-血压乘积。局部心肌灌注明显改善。心室造影显示射血分数显著增加（18%）、心脏指数显著增加（12%）和每搏量指数显著增加（19%）。同时，测得的平均动脉压显著下降约10%，计算得出的外周血管阻力下降约19%。
