The interaction of the calcium antagonist RO 40‐5967 with digoxin.

Abstract

1. The interaction of the newer calcium antagonist Ro 40‐5967 with digoxin was investigated in 42 healthy subjects under steady state conditions. 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 three 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 (Cmax) and AUC. For AUC this effect was significantly dose‐dependent. 4. Increasing doses of the calcium antagonist led 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 was more pronounced when Ro 40‐5967 was added to the medication. No significant changes of stroke volume and blood pressure were noted. 6. In conclusion Ro 40‐5967 led to a significant elevation of the plasma concentration‐time curve (AUC) of digoxin. This effect was dose‐dependent. 1995 The British Pharmacological Society