Kuhlmann J, Marcin S
Klin Wochenschr. 1985 Jul 15;63(14):636-42. doi: 10.1007/BF01732859.
The effect of diltiazem (D) on the pharmacokinetics and pharmacodynamics of beta-acetyldigoxin (AD; n = 12) and digitoxin (DGT; n = 10) was studied in 22 patients with cardiac insufficiency stages II-III by the New York Heart Association. 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 systole 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-administration of 180 mg/day D. In eight patients digoxin plasma levels increased continuously during additional D administration. After reaching a new steady state at 0.93 +/- 0.35 ng/ml digoxin concentrations were at an average 43% higher than before D administration (0.65 +/- 0.27 ng/ml) with a simultaneous increase in renal glycoside excretion. The other four patients showed neither changes in digoxin concentrations in plasma nor in renal glycoside excretion. Only half the patients treated with DGT and D revealed an increase in DGT plasma levels of 21.4%. Daily renal glycoside excretion was not altered by D administration. In accordance to the increasing AD plasma concentration, PQ-interval was prolonged and T-wave flattening was intensified, whereas the systolic time intervals after concomitant treatment of AD and D did not differ from those after AD alone.(ABSTRACT TRUNCATED AT 250 WORDS)
在22例纽约心脏协会心功能II - III级的心力衰竭患者中,研究了地尔硫䓬(D)对β - 乙酰地高辛(AD;n = 12)和洋地黄毒苷(DGT;n = 10)药代动力学和药效学的影响。在联合给予180 mg/天D之前和期间,反复记录糖苷血浆浓度、肾脏排泄以及心电图[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[总机电收缩期指数(QS21)、左心室射血时间指数(LVETI)、射血前期指数(PEPI)、PEP/LVET比值]。8例患者在额外给予D期间地高辛血浆水平持续升高。在达到新的稳态时,地高辛浓度为0.93±0.35 ng/ml,平均比给予D之前(0.65±0.27 ng/ml)高43%,同时肾脏糖苷排泄增加。其他4例患者的地高辛血浆浓度和肾脏糖苷排泄均无变化。仅一半接受DGT和D治疗的患者显示DGT血浆水平升高21.4%。给予D后每日肾脏糖苷排泄未改变。与AD血浆浓度升高一致,PQ间期延长,T波平坦化加剧,而AD与D联合治疗后的收缩期时间间期与单独使用AD后的无差异。(摘要截断于250字)