Dissociation of electrophysiologic and pharmacologic stability during an abbreviated oral loading regimen of amiodarone.
Thirty-three patients treated with an abbreviated oral amiodarone loading regimen for ventricular tachycardia underwent electrophysiologic testing in the control state, after 1 week of high-dose (1170 +/- 88 mg/day) inpatient therapy; and after an 8-week intermediate (669 +/- 129 mg/day) dosing phase. Serum levels of amiodarone and desethylamiodarone were measured by high-pressure liquid chromatography during follow-up electrophysiologic studies. Although the corrected sinus node recovery time, sinoatrial conduction time, and AH and HV intervals remained unchanged throughout the loading period, the sinus cycle length, Wenckebach cycle length, atrial and ventricular refractory periods, and ventricular tachycardia mean and return cycle lengths lengthened significantly by 1 week. They then remained stable for the remainder of the treatment period (control less than 1 and 8 weeks, p less than 0.05). In contrast, amiodarone and especially desethylamiodarone levels rose from 1 to 8 weeks: 1.29 +/- 0.56 to 1.97 +/- 0.90 micrograms/ml (p = 0.001) and 0.63 +/- 0.29 to 1.29 +/- 0.61 micrograms/ml (p less than 0.0001), respectively. Because this regimen produces relatively prompt electrophysiologic changes, which then stabilize, early outpatient management becomes feasible before pharmacologic steady state is attained.
Department of Laboratory Medicine and Pathology, Yale University School of Medicine, New Haven, CT 06510.
L F
LF
Rosenfeld
E E
EE
Kennedy
R A
RA
Perlmutter
M J
MJ
Bookbinder
C A
CA
McPherson
W P
WP
Batsford
D000368:Aged; D000638:Amiodarone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology*; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004594:Electrophysiology; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology
C036116:desethylamiodarone; D000638:Amiodarone