Kuhlmann J, Marcin S, Frank K H
Klin Wochenschr. 1984 May 15;62(10):451-7. doi: 10.1007/BF01726906.
The effect of nifedipine (N) on the pharmacokinetics and pharmacodynamics of beta-acetyldigoxin (AD; n = 11) and digitoxin (DGT; n = 10) was studied in 21 patients with cardiac insufficiency stage II-III NYHA. Glycoside plasma concentration and renal excretion as well as electrocardiogram heart rate, atrioventricular transconduction time (PQ), duration of electrical systole corrected for heart rate (QTc), mean amplitude of T waves in leads V2 to V6 (TV2-6) and systolic time intervals total electromechanical systole index (QS21), left ventricular ejection time index (LVETI), pre-ejection period index (PEPI), PEP/LVET-ratio were recorded repeatedly before and during co-administrations of 40-60 mg/day N. Plasma AD concentrations were 0.64 +/- 0.22 ng/ml (mean +/- SD) before and 0.61 +/- 0.21 ng/ml during co-administration of N over 10-14 days, plasma DGT concentrations 13.9 +/- 4.1 ng/ml before and 13.7 +/- 4.5 ng/ml during co-administration of N over 4-6 weeks. Daily glycoside excretion was not affected by treatment with N. Heart rate and PQ-interval were not significantly changed during co-administration of N whereas T-wave flattening was intensified and QT-duration was lengthened. Concomitant treatment of AD and N led to an increase of PEPI and PEP/LVET compared to AD alone in ten patients whereas the systolic time intervals after concomitant treatment of DGT and N in most patients did not differ from those after DGT alone. From our findings we conclude that N had no clinically significant effect on pharmacokinetics and pharmacodynamics of AD or DGT.
在21例纽约心脏协会(NYHA)心功能II - III级的心力衰竭患者中,研究了硝苯地平(N)对β - 乙酰地高辛(AD;n = 11)和洋地黄毒苷(DGT;n = 10)药代动力学和药效学的影响。在联合服用40 - 60mg/天N之前和期间,反复记录糖苷血浆浓度、肾脏排泄以及心电图的心率、房室传导时间(PQ)、经心率校正的电收缩期持续时间(QTc)、V2至V6导联T波平均振幅(TV2 - 6)和收缩期时间间期总机电收缩指数(QS21)、左心室射血时间指数(LVETI)、射血前期指数(PEPI)、PEP/LVET比值。在联合服用N 10 - 14天期间,血浆AD浓度在联合用药前为0.64±0.22ng/ml(平均值±标准差),联合用药期间为0.61±0.21ng/ml;在联合服用N 4 - 6周期间,血浆DGT浓度在联合用药前为13.9±4.1ng/ml,联合用药期间为13.7±4.5ng/ml。每日糖苷排泄不受N治疗的影响。在联合服用N期间,心率和PQ间期无显著变化,而T波平坦化加剧,QT间期延长。与单独使用AD相比,AD与N联合治疗使10例患者的PEPI和PEP/LVET增加,而在大多数患者中,DGT与N联合治疗后的收缩期时间间期与单独使用DGT后无差异。根据我们的研究结果,我们得出结论,N对AD或DGT的药代动力学和药效学没有临床显著影响。