[Pharmacodynamics and pharmacokinetics of flecainide in cardiac pre-excitation of the bundle of Kent].
In order to identify the flecainide plasma concentrations capable to inhibit the abnormal Kent's pathways, 9 patients affected by a Wolff-Parkinson-White syndrome were studied. One of them (a female 21 years old) previously received 200 mg oral flecainide "una tantum", 8 received 100 mg bid for at least 2 weeks. They had a short PR interval and an evident delta wave on the surface ECG, diagnostic for pre-excitation syndrome. The flecainide plasma half-life calculated in 6 patients chronically treated correlated directly and strictly with age. In all patients the flecainide treatment blocked the conduction through the bundle of Kent (normal PR, no delta wave), then the treatment was stopped and the elimination kinetics of flecainide were studied while a Holter 24h ECG monitoring was performed; thus we could extrapolate the flecainide plasma concentrations at which, during the elimination phase, the PR interval became short and the delta wave reappeared. Since short PR and delta wave are the expression of pre-excitation, we were able to determine the minimum concentrations capable to inhibit conduction through the abnormal bundles (290.0 ng ml-1 in the acutely treated patient and average 275.0 ng ml-1 in the chronically treated patients). These plasma levels are near to the lower therapeutic range accepted for ventricular ectopic arrhythmias (200 divided by 800 ng ml-1). Only larger studies will indicate if a relationship exists between the blockade of abnormal pathways and the preventive effect of flecainide on arrhythmias of Wolff-Parkinson-White syndrome. Another open question is whether a simple, non-invasive pharmacodynamic and pharmacokinetic procedure like that one described in the present paper can be used to predict the efficacy of treatment in patients with cardiac pre-excitation.
Casiglia
E
E
Padrini
R
R
Piovan
D
D
Marchese
D
D
Sforza
G
G
Martines
C
C
Pessina
A C
AC
D000328:Adult; D000368:Aged; D005260:Female; D005424:Flecainide / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014927:Wolff-Parkinson-White Syndrome / Q000097:blood / Q000209:etiology / Q000503:physiopathology*
D005424:Flecainide
Farmacodinamica e farmacocinetica della flecainide nella pre-eccitazione cardiaca da fasci di Kent.