The pharmacodynamic and pharmacokinetic interaction between single doses of flecainide acetate and verapamil: effects on cardiac function and drug clearance

Clinical Pharmacology and Therapeutics
J L HoltzmanA M Miller

Abstract

Flecainide and verapamil are antiarrhythmic agents that may be used in combination. We have examined their pharmacodynamic interaction by M-mode echocardiography and electrocardiography in eight normal male volunteers (24 +/- 1.8 years of age). Flecainide decreased the left ventricular ejection fraction (LVEF) (-4.4 +/- 1.2%, p less than 0.008), but verapamil did not. Neither drug affected cardiac output or vascular resistance. Both drugs increased the PR interval (12 +/- 4 msec, p less than 0.01 for flecainide; 12 +/- 5, p less than 0.04 for verapamil). Flecainide, but not verapamil, increased the QTc interval (23 +/- 8 msec, p less than 0.02). Both drugs also increased the systolic time interval ratio (PEPc/LVETc) (0.074 +/- 0.012, p less than 0.0004 for flecainide; 0.029 +/- 0.008, p less than 0.007 for verapamil). The combination of flecainide and verapamil had additive effects on myocardial contractility and on atrioventricular conduction. Verapamil slightly decreased the plasma clearance of flecainide (7.78 +/- 0.60 ml/kg/min for flecainide alone, 7.34 +/- 0.48 ml/kg/min for flecainide and verapamil together, p less than 0.05). On the other hand, flecainide had no effect on the plasma clearance of verapamil, which suggest...Continue Reading

Citations

Dec 1, 1991·Journal of Pharmacokinetics and Biopharmaceutics·D Verotta, L B Sheiner
Oct 31, 2003·Expert Opinion on Drug Safety·Renke Maas, Rainer H Böger
Dec 17, 1992·The New England Journal of Medicine·J BussD L Heene
Jun 1, 2015·Journal of Pharmacological and Toxicological Methods·Rob WallisHelen Maddock
May 1, 2021·Journal of Clinical Medicine·Carlo LavalleRenato Pietro Ricci
May 19, 2021·Journal of Molecular and Cellular Cardiology·Pei-Chi YangColleen E Clancy
Aug 8, 2021·BMJ Case Reports·Dario Manley-CascoSteven Girard

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