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

Br J Clin Pharmacol. 1995 May;39(5):491-6. doi: 10.1111/j.1365-2125.1995.tb04485.x.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / pharmacology*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / pharmacology*
  • Cardiac Output / drug effects
  • Digoxin / administration & dosage
  • Digoxin / blood
  • Digoxin / pharmacokinetics*
  • Digoxin / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Electrocardiography / drug effects
  • Fluorescence Polarization
  • Heart Rate / drug effects
  • Humans
  • Male
  • Mibefradil
  • Stroke Volume / drug effects
  • Tetrahydronaphthalenes / administration & dosage
  • Tetrahydronaphthalenes / pharmacology*
  • Ultrasonography, Doppler

Substances

  • Benzimidazoles
  • Calcium Channel Blockers
  • Tetrahydronaphthalenes
  • Mibefradil
  • Digoxin