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  • Title: Metabolite cumulation during chronic propafenone dosing in arrhythmia.
    Author: Kates RE, Yee YG, Winkle RA.
    Journal: Clin Pharmacol Ther; 1985 Jun; 37(6):610-4. PubMed ID: 4006362.
    Abstract:
    The cumulation of propafenone and two of its metabolites, 5-hydroxypropafenone (5-OHP) and N-depropylpropafenone (NDPP), was examined in patients with frequent ventricular ectopy. After 2 weeks of propafenone therapy (300 mg twice a day), propafenone was discontinued and blood samples were drawn for 24 hours. The mean (+/- SD) steady-state concentrations of propafenone, 5-OHP, and NDPP were 1010 +/- 411, 174 +/- 113, and 179 +/- 93 ng/ml. The concentration ratios of 5-OHP/propafenone and NDPP/propafenone were 0.177 +/- 0.049 and 0.227 +/- 0.203. Plasma concentrations of 5-OHP and NDPP did not decay in a log-linear manner during the sampling period and thus estimates of their disappearance t1/2s were not possible. At 24 hours after propafenone dosing, concentrations of 5-OHP and NDPP were 63% +/- 37% and 50% +/- 21% of their mean steady-state levels. Our data indicate that these propafenone metabolites cumulate in the plasma during chronic oral propafenone therapy, and that their clinical role needs to be elucidated.
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