Department of Pharmacology, AMC MET Medical College and Smt. NHL Medical College, Ahmedabad, India.
Indian J Pharmacol. 2010 Dec;42(6):366-9. doi: 10.4103/0253-7613.71919.
The study was designed to establish relationship between the plasma concentration and QTc interval prolonging effect of fexofenadine and demonstrate the phenomenon of anticlockwise hysteresis.
Six subjects were given fexofenadine 60 mg tablet orally under stable conditions, and their drug concentrations were measured at regular intervals. At predetermined time, their ECGs were recorded. Data were analyzed and plotted graphically.
Randomized parallel design, single group study conducted at clinical research organization of Ahmadabad.
In all subjects time taken for maximum plasma concentration of fexofenadine (T(max)) was around 3 h and the value of average maximum plasma concentration was 460.63 ng/mL, the effect of fexofenadine on the heart (measured as QTc interval prolongation) was maximum (E(max)) after 6 h and average QTc interval was 469.75 ms. Thus, the time to maximum concentration of fexofenadine did not match with the maximum effect on the heart as measured by QTc interval.
The relationship between the drug concentration and drug effect on the heart are at two different time scales. It can be understood by two-compartment model of pharmacokinetics, and this retardation or lagging of an effect behind the concentration is known as hysteresis. The increase of QTc was not beyond 500 ms and not sustained, demonstrating overall cardiac safety of fexofenadine.
本研究旨在建立非索非那定的血浆浓度与 QTc 间期延长效应之间的关系，并证明其具有反时钟滞后现象。
6 名受试者在稳定状态下口服给予非索非那定 60mg 片剂，并定期测量其药物浓度。在预定时间记录心电图。对数据进行分析和图形绘制。
随机平行设计，在艾哈迈达巴德的临床研究机构进行的单组研究。
在所有受试者中，非索非那定的最大血浆浓度达峰时间（T(max)）约为 3 小时，平均最大血浆浓度值为 460.63ng/mL，非索非那定对心脏的作用（以 QTc 间期延长来衡量）在 6 小时时达到最大（E(max)），平均 QTc 间期为 469.75ms。因此，非索非那定的达峰时间与 QTc 间期测量的心脏最大效应并不匹配。
药物浓度与心脏药物效应之间存在两个不同的时间尺度。这可以通过药代动力学两室模型来理解，这种浓度滞后或延迟效应称为滞后。QTc 的增加不超过 500ms 且不持续，表明非索非那定具有整体心脏安全性。
