Pharmacokinetics and Pharmacodynamics of Propafenone During Acute and Chronic Administration

Overview

Journal Eur J Clin Pharmacol

Specialty Pharmacology

Date 1988 Jan 1

PMID 3383990

Citations 6

Authors

P Giani

M Landolina

V Giudici

C Bianchini

G Ferrario

S Marchi

E Riva

R Latini

Affiliations

Soon will be listed here.

Abstract

The pharmacokinetics of propafenone and 5-OH-propafenone and their relationship with the antiarrhythmic action and side effects have been studied in 10 patients with stable, frequent, premature ventricular beats (224-928 premature ventricular complexes/h). Observations were made after a single dose of propafenone 300 mg p.o., and after 1 and 3 months (only 5 out of 10 patients) of therapy with 300 mg t.d.s. After 1 month of treatment the plasma elimination half-life of propafenone (6.7 h) was almost twice as long as after a single dose (3.5 h), and the area under the plasma propafenone concentration-time curve (7620 ng.ml-1.h) was significantly larger than after single dose (3522 ng.ml-1.h); this was also true for the metabolite. The ratio of the AUCs of 5-OH-propafenone and propafenone decreased from the single dose (0.63) to 1 month (0.32). These variables remained stable up to 3 months. Eight patients had greater than or equal to 75% reduction of premature ventricular complexes after 3 days of therapy, and in 7 they were completely suppressed; the response was maintained over 1 to 3 months. Side effects were minor and in no case had the drug to be withdrawn or the dose reduced. Thus, the kinetics of propafenone were time-dependent. Its active metabolite did not accumulate greatly during chronic treatment. The lasting antiarrhythmic effect observed in some patients suggests a b.d.s. regimen instead of t.d.s. dosing in selected patients.

Citing Articles

Stereoselective steady state disposition and action of propafenone in Chinese subjects.

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Propafenone. A reappraisal of its pharmacology, pharmacokinetics and therapeutic use in cardiac arrhythmias.

Bryson H, Palmer K, Langtry H, Fitton A Drugs. 1993; 45(1):85-130.

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Nonlinear kinetics of propafenone metabolites in healthy man.

Vozeh S, HAEFELI W, Ha H, Vlcek J, Follath F Eur J Clin Pharmacol. 1990; 38(5):509-13.

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Minimal effective concentration values of propafenone and 5-hydroxy-propafenone in acute and chronic therapy.

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References

COUMEL P, Leclercq J, Assayag P . European experience with the antiarrhythmic efficacy of propafenone for supraventricular and ventricular arrhythmias. Am J Cardiol. 1984; 54(9):60D-66D. DOI: 10.1016/s0002-9149(84)80288-x. View

McLeod A, Stiles G, SHAND D . Demonstration of beta adrenoceptor blockade by propafenone hydrochloride: clinical pharmacologic, radioligand binding and adenylate cyclase activation studies. J Pharmacol Exp Ther. 1984; 228(2):461-6. View

Connolly S, Lebsack C, Winkle R, Harrison D, Kates R . Propafenone disposition kinetics in cardiac arrhythmia. Clin Pharmacol Ther. 1984; 36(2):163-8. DOI: 10.1038/clpt.1984.157. View

Kates R, Yee Y, Winkle R . Metabolite cumulation during chronic propafenone dosing in arrhythmia. Clin Pharmacol Ther. 1985; 37(6):610-4. DOI: 10.1038/clpt.1985.97. View

Ledda F, Mantelli L, Manzini S, Amerini S, Mugelli A . Electrophysiological and antiarrhythmic properties of propafenon in isolated cardiac preparations. J Cardiovasc Pharmacol. 1981; 3(6):1162-73. DOI: 10.1097/00005344-198111000-00002. View

Siddoway L, Roden D, Woosley R . Clinical pharmacology of propafenone: pharmacokinetics, metabolism and concentration-response relations. Am J Cardiol. 1984; 54(9):9D-12D. DOI: 10.1016/s0002-9149(84)80278-7. View

Podrid P, LOWN B . Propafenone: a new agent for ventricular arrhythmia. J Am Coll Cardiol. 1984; 4(1):117-25. DOI: 10.1016/s0735-1097(84)80328-9. View

Connolly S, Kates R, Lebsack C, Harrison D, Winkle R . Clinical pharmacology of propafenone. Circulation. 1983; 68(3):589-96. DOI: 10.1161/01.cir.68.3.589. View

Naccarella F, BRACCHETTI D, Palmieri M, Marchesini B, Ambrosioni E . Propafenone for refractory ventricular arrhythmias: correlation with drug plasma levels during long-term treatment. Am J Cardiol. 1984; 54(8):1008-14. DOI: 10.1016/s0002-9149(84)80135-6. View

10.

Latini R, Sica A, Marchi S, Chen Z, Gavinelli M, Benfenati E . High-performance liquid chromatographic separation and mass spectrometric identification of propafenone, 5-hydroxypropafenone and N-depropylpropafenone. J Chromatogr. 1988; 424(1):211-4. DOI: 10.1016/s0378-4347(00)81097-x. View

11.

Hege H, Hollmann M, Kaumeier S, LIETZ H . The metabolic fate of 2H-labelled propafenone in man. Eur J Drug Metab Pharmacokinet. 1984; 9(1):41-55. DOI: 10.1007/BF03189604. View

12.

Breithardt G, Borggrefe M, Wiebringhaus E, Seipel L . Effect of propafenone in the Wolff-Parkinson-White syndrome: electrophysiologic findings and long-term follow-up. Am J Cardiol. 1984; 54(9):29D-39D. DOI: 10.1016/s0002-9149(84)80283-0. View

13.

Hammill S, Sorenson P, Wood D, Sugrue D, Osborn M, Gersh B . Propafenone for the treatment of refractory complex ventricular ectopic activity. Mayo Clin Proc. 1986; 61(2):98-103. DOI: 10.1016/s0025-6196(12)65194-5. View

14.

Salerno D, Granrud G, Sharkey P, Asinger R, Hodges M . A controlled trial of propafenone for treatment of frequent and repetitive ventricular premature complexes. Am J Cardiol. 1984; 53(1):77-83. DOI: 10.1016/0002-9149(84)90687-8. View

15.

von Philipsborn G, Gries J, Hofmann H, KREISKOTT H, Kretzschmar R, Muller C . Pharmacological studies on propafenone and its main metabolite 5-hydroxypropafenone. Arzneimittelforschung. 1984; 34(11):1489-97. View

16.

Heger J, Hubbard J, Zipes D, Miles W, Prystowsky E . Propafenone treatment of recurrent ventricular tachycardia: comparison of continuous electrocardiographic recording and electrophysiologic study in predicting drug efficacy. Am J Cardiol. 1984; 54(9):40D-44D. DOI: 10.1016/s0002-9149(84)80284-2. View

17.

Rocchetti M, Recchia M . SPBS: statistical programs for biological sciences. Minicomputer software for applying routine biostatistical methods. Comput Programs Biomed. 1982; 14(1):7-20. DOI: 10.1016/0010-468x(82)90084-8. View

18.

Dinh H, Murphy M, Baker B, DeSoyza N, Franciosa J . Efficacy of propafenone compared with quinidine in chronic ventricular arrhythmias. Am J Cardiol. 1985; 55(13 Pt 1):1520-4. DOI: 10.1016/0002-9149(85)90965-8. View

19.

Connolly S, Kates R, Lebsack C, Echt D, Mason J, Winkle R . Clinical efficacy and electrophysiology of oral propafenone for ventricular tachycardia. Am J Cardiol. 1983; 52(10):1208-13. DOI: 10.1016/0002-9149(83)90575-1. View

20.

Hollmann M, BRODE E, Hotz D, Kaumeier S, Kehrhahn O . Investigations on the pharmacokinetics of propafenone in man. Arzneimittelforschung. 1983; 33(5):763-70. View