The interaction of the calcium antagonist RO 40-5967 with digoxin.
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.
Siepmann
M
M
Department of Clinical Pharmacology and Therapeutics, Medical Hospital, Technical University, Dresden, Germany.
Kleinbloesem
C
C
Kirch
W
W
D000284:Administration, Oral; D000328:Adult; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004562:Electrocardiography / Q000187:drug effects; D005454:Fluorescence Polarization; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D020748:Mibefradil; D013318:Stroke Volume / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D018608:Ultrasonography, Doppler
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D020748:Mibefradil; D004077:Digoxin