Chronic lorcainide therapy for symptomatic premature ventricular complexes: efficacy, pharmacokinetics and evidence for norlorcainide antiarrhythmic effect.
Chronic premature ventricular complexes (PVCs) have been effectively suppressed by oral lorcainide as reported in previous short-term studies. The plasma level-effect relation of lorcainide may be affected by the possible cardioactivity of norlorcainide, a metabolite that accumulates after repeated oral doses. This study evaluated the long-term efficacy of lorcainide in suppressing chronic symptomatic PVCs, and examined the relation of arrhythmia suppression to plasma concentrations of lorcainide and norlorcainide. Fourteen patients were treated with lorcainide, 200 to 400 mg/day, 12 of whom achieved nearly complete suppression of arrhythmias after treatment for 1 year. Chronic lorcainide treatment was well tolerated; no patient discontinued treatment because of adverse effects. Lorcainide and norlorcainide plasma concentrations remained stable after the first week of therapy. Antiarrhythmic activity persisted throughout the year. Upon drug withdrawal, the mean lorcainide washout half-life was 14.3 +/- 3.7 hours and the mean norlorcainide washout half-life was 31.9 +/- 8.9 hours. The return of arrhythmias occurred well after the lorcainide plasma concentration had decreased to subtherapeutic levels, suggesting an antiarrhythmic effect of norlorcainide. Thus, long-term lorcainide therapy is effective in treating chronic symptomatic PVCs and is well tolerated by most patients. The metabolite norlorcainide appears to have antiarrhythmic activity independent of lorcainide.
Mead
R H
RH
Keefe
D L
DL
Kates
R E
RE
Winkle
R A
RA
D044482:Benzeneacetamides; D005117:Cardiac Complexes, Premature / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D006207:Half-Life; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D013997:Time Factors
D044482:Benzeneacetamides; D010880:Piperidines; C031145:norlorcainide; C015970:lorcainide