THE INTERACTION OF THE CALCIUM-ANTAGONIST RO-40-5967 WITH DIGOXIN

1 The interaction of the newer calcium antagonist Ro 40-5967 with digo xin was investigated in 42 healthy subjects under steady state conditi ons. 2 After an adequate loading dose digoxin 0.375 mg once daily was given alone for 1 week. Afterwards three different doses (50, 100, 150 mg daily) of the calcium antagonist Ro 40-5967 were administered to t hree groups of 14 subjects each for 1 week concurrently with digoxin 0 .375 mg daily. 3 Ro 40-5967 led to an increase of mean maximum digoxin plasma concentrations (C-max) and AUC. For AUC this effect was signif icantly dose-dependent. 4 Increasing doses of the calcium antagonist l ed to a stepwise rise of the PQ-time in ECG. 5 A slight fall of heart rate was seen after a 7 day treatment of digoxin alone. This effect wa s more pronounced when Ro 40-5967 was added to the medication. No sign ificant changes of stroke volume and blood pressure were noted. 6 In c onclusion Ro 40-5967 led to a significant elevation of the plasma conc entration-time curve (AUG) of digoxin. This effect was dose-dependent.