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Metabolite cumulation during chronic propafenone dosing in arrhythmia
Author(s) -
Kates Robert E,
Yee Yin Gail,
Winkle Roger A
Publication year - 1985
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1985.97
Subject(s) - propafenone , metabolite , dosing , active metabolite , medicine , pharmacokinetics , pharmacology , oral dose , plasma concentration , atrial fibrillation
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 t½s 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. Clinical Pharmacology and Therapeutics (1985) 37 , 610–614; doi: 10.1038/clpt.1985.97