Serum digoxin concentrations during ethmozine antiarrhythmic therapy.
The potential for pharmacokinetic drug interaction between ethmozine (moricizine HCl), a phenothiazine class I antiarrhythmic investigational drug, and digoxin was evaluated in 13 cardiac patients with normal renal function. Antiarrhythmic therapy was initiated in patients with potentially lethal (nonlife-threatening) ventricular arrhythmias (greater than 30 ventricular ectopic beats [VEB]/hr) who were receiving maintenance digoxin therapy for congestive heart failure and/or atrial fibrillation. Serum digoxin concentrations of patients were measured frequently by radioimmunoassay and plasma ethmozine concentrations by high-performance liquid chromatographic methods. Patients entered a short-term (4 weeks) single-blind, placebo controlled ethmozine protocol with an option to receive long-term (1 to 6 months) open-label maintenance ethmozine therapy. Ambulatory ECGs (48 hour) used to assess antiarrhythmic efficacy of ethmozine during each week of the short-term protocol showed that 77% of patients demonstrated greater than 90% mean hourly frequency suppression of all forms of ventricular ectopy. Serum digoxin concentrations during short-term ethmozine dosing showed a nonsignificant (p greater than 0.05) increase of 10% to 15% (mean 0.91 ng/ml to 1.13 ng/ml). The short-term protocol serum digoxin levels correlated closely with serum digoxin concentrations during placebo therapy (1st week, r = 0.90; 2nd week, r = 0.87). Serum digoxin concentrations were not significantly different (p greater than 0.05) from placebo values at the end of 1, 3, and 6 months of maintenance ethmozine therapy. Thus, we conclude that ethmozine administered in an antiarrhythmic efficacious dosage (10 mg/kg/day) showed no important clinical or statistically significant change in serum digoxin concentrations of cardiac patients with normal renal function.
Kennedy
H L
HL
Sprague
M K
MK
Redd
R M
RM
Wiens
R D
RD
Blum
R I
RI
Buckingham
T A
TA
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000188:drug therapy; D005117:Cardiac Complexes, Premature / Q000097:blood / Q000150:complications / Q000188:drug therapy; D002986:Clinical Trials as Topic; D004077:Digoxin / Q000097:blood* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D016293:Moricizine; D010640:Phenothiazines / Q000097:blood / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D010640:Phenothiazines; D016293:Moricizine; D004077:Digoxin