Pharmacokinetics and pharmacodynamics of propafenone during acute and chronic administration

P. Giani, M. Landolina, V. Giudici, C. Bianchini, G. Ferrario, S. Marchi, E. Riva, R. Latini

Research output: Contribution to journalArticle

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 ≧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 Side effects were minor and in no case had the drug to be withdrawn or the dose reduced.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.

Original languageEnglish
Pages (from-to)187-194
Number of pages8
JournalEuropean Journal of Clinical Pharmacology
Volume34
Issue number2
DOIs
Publication statusPublished - Mar 1988

Keywords

  • 5-OH-propafenone
  • antiarrhythmic effect
  • chronic treatment
  • pharmacokinetics
  • propafenone

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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