Plasma propafenone concentration in the evaluation of anti-arrhythmic efficacy.
The anti-arrhythmic drug efficacy of oral propafenone therapy (300 mg to 900 mg per day) was studied in relation to propafenone and hydroxy-propafenone plasma concentrations in 70 outpatients (46 males, 24 females, mean age 57 +/- 12 years) followed up for 24 +/- 32 months. On average 1.7 plasma concentration measurements were performed per patient. The arrhythmias were effectively controlled in 32 patients, but in another 32 patients propafenone therapy was ineffective; in six patients the evaluation was unclear. The therapy was effective in 66% of patients with ventricular premature beats, in 50% with complex ventricular arrhythmias, in 40% with ventricular tachycardia and in 20% with supraventricular tachycardia. Fifty per cent of patients with coronary heart disease and electrical disease, but only 20% with dilated cardiomyopathy and Wolff-Parkinson-White syndrome were effectively treated. Measurement of peak plasma propafenone levels performed 4.5 +/- 2 h after oral drug administration revealed no statistically significant dose-plasma concentration relation. Optimal propafenone drug efficacy was documented at propafenone plasma concentrations ranging from 0.20 to 0.60 micrograms/ml (63% of patients considered as effectively treated). There was a trend to decrease propafenone efficacy at plasma concentrations below 0.20 micrograms/ml and above 0.60 micrograms/ml. Analysis of hydroxypropafenone identified four patients as poor metabolizers with unusually high propafenone and low hydroxypropafenone plasma concentrations; only one of these four patients showed drug efficacy. Monitoring of propafenone and hydroxypropafenone plasma concentrations was a practical procedure to assess patient's compliance, to identify poor metabolizers and to guide anti-arrhythmic drug therapy.
Steurer
G
G
Kardiologische Universitätsklinik, Vienna, Austria.
Weber
H
H
Schmidinger
H
H
Plass
H
H
Frey
B
B
Pürerfellner
H
H
Probst
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016009:Chi-Square Distribution; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011405:Propafenone / Q000031:analogs & derivatives / Q000097:blood* / Q000627:therapeutic use*; D016277:Ventricular Function, Left
D011405:Propafenone; C044307:5-hydroxypropafenone