Plasma Concentrations of Propafenone and 5-hydroxypropafenone and their Relationship to the Efficacy against Ventricular Arrhythmia Masashi Horimoto 1 , Masafumi Fujiwara 1 , Ken-ichi Koguchi 2 , Keiichi Igarashi 2 , Takashi Takenaka 2 1Division of Cardiology, Sapporo National Hospital 2Division of Internal Medicine, Ishikari Hospital Keyword: プロパフェノン , 5-ヒドロキシプロパフェノン , 薬物血漿濃度 , 抗不整脈効果 , 心室性期外収縮 , propafenone , 5-hydroxypropafenone , drug plasma concentration , anti-arrhythmic effect , ventricular arrhythmia pp.1189-1193
Published Date 1996/11/15
DOI https://doi.org/10.11477/mf.1404901370
  • Abstract
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Caucasian population includes 7 to 10% of poor metabolizers for propafenone (PF) due to an absence of hepatic cytochrome P-450 enzyme. Earlier studies on Caucasian population have demonstrated no positive correlation between plasma concentrations of propafenone (PF) and 5-hydroxypropaphenone (5-HP) and no clear relationship between the concentrations and the anti-arrhythmic efficacy of PF. To delineate those relationships in Japanese population in which no poor metabolizers are included, consecutive 22 patients with premature ventricular complexes (PVCs)>4000/ day and without organic heart disease were studied. As the efficacy of PF against ventricular arrhythmia a percent reduction in daily frequency of PVCs was evaluated from mandatory 24-hour Holter monitoring before and after the postprandial administration of PF with 450 mg/day. The plasma concentrations of PF and5-HP were determined in the blood collected 2 hours after the administration of PF.

The mean percent reduction in the daily frequency of PVCs after the therapy with PF was 75.6%. The plasma concentration of PF ranged widely from 29-1033 ng/ml (347±291ng/ml, mean±SD) and that of 5-HP ranged from 27-351ng/ml (132±81 ng/ml). A linear relation with Y=0.25X +45.498 was found between the plasma concentrations of PF and 5-HP. Two distinctly different groups were noted in the relationship between the plasma concentrations of PF and 5-HP and the percent reduction in the daily frequency of PVCs. One group showed>80% reduction in PVCs, regardless of the plasma concentrations of PF and 5-HP. The other group showed a linear relation between the percent reduction in PVCs and the plasma concentrations of PFand 5-HP.

The linear correlation between the plasma concentra-tions of PF and 5-HP is likely due to an absence of poor metabolizers and probably homogeneous activity of hepatic cytochrome P-450 enzyme in Japanese popula-tion. The presence of distinguished two groups on the relationship between the plasma concentrations and the anti-arrhythmic efficiency of PF implicated that anti-arrhythmic efficiency of PF depends on not only plasma concentrations of PF and 5-HP but possibly on the variation of cardiac sensitivity to PF and 5-HP.

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