The interaction of the calcium antagonist RO 40-5967 with digoxin. 1995

M Siepmann, and C Kleinbloesem, and W Kirch
Department of Clinical Pharmacology and Therapeutics, Medical Hospital, Technical University, Dresden, Germany.

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.

UI MeSH Term Description Entries
D008297 Male Males
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D002302 Cardiac Output The volume of BLOOD passing through the HEART per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with STROKE VOLUME (volume per beat). Cardiac Outputs,Output, Cardiac,Outputs, Cardiac
D004077 Digoxin A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666) Digacin,Digitek,Digoregen,Digoxina Boehringer,Digoxine Nativelle,Dilanacin,Hemigoxine Nativelle,Lanacordin,Lanicor,Lanoxicaps,Lanoxin,Lanoxin-PG,Lenoxin,Mapluxin,Boehringer, Digoxina,Lanoxin PG,Nativelle, Digoxine,Nativelle, Hemigoxine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004562 Electrocardiography Recording of the moment-to-moment electromotive forces of the HEART as projected onto various sites on the body's surface, delineated as a scalar function of time. The recording is monitored by a tracing on slow moving chart paper or by observing it on a cardioscope, which is a CATHODE RAY TUBE DISPLAY. 12-Lead ECG,12-Lead EKG,12-Lead Electrocardiography,Cardiography,ECG,EKG,Electrocardiogram,Electrocardiograph,12 Lead ECG,12 Lead EKG,12 Lead Electrocardiography,12-Lead ECGs,12-Lead EKGs,12-Lead Electrocardiographies,Cardiographies,ECG, 12-Lead,EKG, 12-Lead,Electrocardiograms,Electrocardiographies, 12-Lead,Electrocardiographs,Electrocardiography, 12-Lead
D005454 Fluorescence Polarization Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. Anisotropy, Fluorescence,Fluorescence Anisotropy,Polarization, Fluorescence,Anisotropies, Fluorescence,Fluorescence Anisotropies,Fluorescence Polarizations,Polarizations, Fluorescence
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse

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