Investigations on the pharmacokinetics of propafenone in man.

ABSTRACT

The pharmacokinetics of propafenone (Rytmonorm) was studied in 19 healthy volunteers. Propafenone was given intravenously (commercial ampoules of 70 mg) and orally in different doses (150, 300, 450 mg) and forms (solution, commercial film tablets). The results show a dose dependence of bioavailability and maximum plasma concentrations after oral application with over-proportionate increase at higher dose levels yielding bioavailabilities up to 40-50% with single applications of 450 mg. This is interpreted as saturability of a presystemic mechanism during invasion (most probably of the metabolizing enzyme systems of the liver). The mean rate constant of elimination after intravenous application is beta = 0.28 h-1 (95% confidence limits 0.24-0.33 h-1) corresponding to a half-life of 2.5 h. There are no significant differences in these values after oral application and different dosages. The total plasma clearance of 1.0 1/min (95% confidence limits 0.9-1.1 1/min) is almost exclusively metabolic. After 12 days of oral dosing (2 tablets of 150 mg propafenone daily) no statistically significant changes of kinetic parameters could be demonstrated although with some volunteers the total clearance decreased. It is considered that in some persons with relatively low clearance the plasma concentrations may reach levels at which a saturation of enzymatic reactions of metabolism may become relevant even after application of such low single doses as 150 mg.