Digoxin and bepridil: Pharmacokinetic and pharmacodynamic interactions

Publisher Website
Google Scholar
Abstract
The influence of bepridil on steady-state serum digoxin concentrations (SDCs) and the pharmacodynamic actions of both drugs were tested in 48 healthy subjects in a randomized, double-blind study. Subjects were assigned to one of two groups of 24 subjects each: One group received placebo 1, while the other received digoxin, 0.375 mg/day, loaded with doubled doses on days 1 and 2, for 14 days. After 7 days the groups were subdivided into four groups of 12 subjects each and received concurrent dosing of digoxin with either placebo 2 or bepridil, 300 mg/day, loaded with 900 mg on day 8. Mean (.+-. SD) SDCs rose during concurrent bepridil dosing from 0.93 .+-. 0.22 to 1.25 ng/ml (P < 0.001). Noninvasive cardiovascular parameters from ECG, systolic time intervals, and electrical impedance cardiography were not influenced by the placebos. Digoxin and bepridil reduced heart rate and prolonged the PQ interval because of negative chronotropic and dromotropic properties. Positive inotropism from digoxin shortened the corrected electomechanical systole (QS2c) and the preejection period and increased impedance cardiography [(dZ/dt)/RZ index]; the opposite effects occurred after bepridil, indicating negative inotropism. The QT interval corrected for heart rate (QTc) showed a similar pattern of changes, as did QS2c for each drug. Concurrent dosing of both drugs resulted in an addition of their chronotropic effects, whereas the dromotropic effects of each drug alone was not intensified. The strengthened digoxin effect from the increased SDC diminished the negative inotropic effect of bepridil. Overall, drug coadministration resulted in a nearly unchanged digoxin-induced positive inotropism. In relation to the pretreatment value, QTc was only moderately prolonged after concurrent dosing; however, there was strong effect evident on the basis of the previous digoxin-shortened interval. Patients receiving digoxin and bepridil should be monitored carefully, but a general reduction in digoxin dosages does not seem necessary.

This publication has 18 references indexed in Scilit: