Flecainide enantiomers: disposition in human subjects and electrophysiologic actions in vitro

Clinical Pharmacology and Therapeutics
H K KroemerD M Roden

Abstract

The antiarrhythmic agent flecainide is administered as a racemate. The disposition of the individual enantiomers and their electrophysiologic actions are unknown. We therefore determined through plasma levels of S-(+)-flecainide and R-(-)-flecainide in 13 patients who were receiving long-term oral flecainide therapy. In addition, the effects of the enantiomers on action potential characteristics in canine cardiac Purkinje fibers were assessed. Plasma concentrations of R-(-)flecainide were significantly higher than those of the S-(+)-enantiomer (-/+ ratio, 1.10 +/- 0.13,mean +/- SD; range, 0.89 to 1.32, p less than 0.01), suggesting that the drug undergoes enantioselective disposition. In the in vitro experiments, both enantiomers reduced phase 0 action potential Vmax (an index of the fast inward sodium current) and shortened action potential duration at 50% and 90% repolarization, but no differences between the enantiomers were detected. The time constants for development of Vmax depression were significantly longer for S-(+)-flecainide (13.4 +/- 1.5 seconds) compared with R-(-)-flecainide (8.9 +/- 0.6 seconds, p less than 0.001). Thus, although S-(+)-flecainide and R-(-)-flecainide undergo modest enantioselective disposition, ...Continue Reading

Citations

Jul 1, 1992·Journal of Clinical Pharmacology·R L Williams
Mar 1, 1992·British Journal of Clinical Pharmacology·U M BirgersdotterD M Roden
Jan 1, 1992·European Journal of Clinical Pharmacology·A MunafoJ Biollaz
Nov 6, 1998·British Journal of Clinical Pharmacology·T J Campbell, K M Williams
Feb 19, 1993·Pharmacy World & Science : PWS·D T WitteR A De Zeeuw

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