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

Jordan L. Holtzman, Denise Finley, Linda Mottonen, Donald A. Berry, Bruce P. Ekholm, Donald C. Kvam, Roy L. McQuinn, A. M. Miller

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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 < 0.008), but verapamil did not. Neither drug affected cardiac output or vascular resistance. Both drugs increased the PR interval (12 ± 4 msec, p < 0.01 for flecainide; 12 ± 5, p < 0.04 for verapamil). Flecainide, but not verapamil, increased the QTc interval (23 ± 8 msec, p < 0.02). Both drugs also increased the systolic time interval ratio (PEPc/LVETc)(0.074 ± 0.012, p < 0.0004 for flecainide; 0.029 ± 0.008, p < 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 < 0.05). On the other hand, flecainide had no effect on the plasma clearance of verapamil, which suggests that there was little interaction between the two drugs on their pharmacokinetic parameters.

Original languageEnglish (US)
Pages (from-to)26-32
Number of pages7
JournalClinical pharmacology and therapeutics
Volume46
Issue number1
DOIs
StatePublished - Jul 1989

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