Metabolite cumulation during chronic propafenone dosing in arrhythmia.
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.
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000378:metabolism* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011405:Propafenone / Q000031:analogs & derivatives; D011427:Propiophenones / Q000378:metabolism* / Q000627:therapeutic use; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D011427:Propiophenones; D011405:Propafenone; C044307:5-hydroxypropafenone; C045806:N-depropylpropafenone