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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Pharmacokinetic and pharmacodynamic evaluation of propafenone in patients with ventricular arrhythmia. Propafenone Research Group.

Propafenone, a class IC antiarrhythmic agent, is metabolized into two active metabolites: 5-hydroxypropafenone (5-OHP) and N-depropylpropafenone (NDPP). In a placebo-controlled, double-blind study, we examined trough plasma concentrations of propafenone and its two metabolites in 169 subjects. Patients were randomized to one of five parallel treatment groups: placebo and 337.5, 450, 675, or 900 mg/day propafenone with 24-hour ambulatory ECG monitorings, 12-lead ECGs, and plasma samples obtained at frequent intervals. Nonlinear kinetics were noted for propafenone and NDPP but not for 5-OHP. The ratio of NDPP to propafenone was about 10% at all doses, but the ratio of 5-OHP to propafenone decreased from 33% at 337.5 mg/day to 18% at 900 mg/day. Propafenone suppression of ventricular ectopy was dependent on concentration, with pairs and VT beats selectively suppressed at lower concentrations than VPBs. The PR interval and QRS duration increased significantly at propafenone concentrations above 100 ng/ml, while minimal heart rate slowing was noted at concentrations above 1,000 ng/ml.[1]


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