Comparison of the pharmacodynamic effects of intravenous and oral propafenone.
The effect of propafenone and its major metabolite 5-hydroxy-propafenone on ECG intervals was investigated in eight healthy extensive metabolizers after single oral (300 to 450 mg) and intravenous (35 to 50 mg) doses of propafenone in a single-blind randomized trial. Peak serum concentrations were 278 +/- 233 ng/ml (oral) and 295 +/- 131 ng/ml (intravenous). After oral administration peak 5-hydroxy-propafenone levels were 194 +/- 65 ng/ml, whereas after intravenous dosing no metabolite was detected, except in one subject. Serum concentrations were related to effects by linear regression including a hypothetical effect-site compartment in a pharmacokinetic-pharmacodynamic model. Significant prolongations of ECG intervals were found in both sequences. Comparison of the two concentration-effect data sets (intravenous, oral) revealed an additive effect of 5-hydroxy-propafenone in four of eight subjects for PQ interval and seven of eight subjects for QRS duration. We conclude that 5-hydroxy-propafenone exerts pharmacologic activity and could thus contribute to the antiarrhythmic effect of propafenone.
Department of Internal Medicine, Kantonsspital Basel, Switzerland.
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Follath
D000284:Administration, Oral; D000328:Adult; D004341:Drug Evaluation; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D011405:Propafenone / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D011897:Random Allocation
D011405:Propafenone