Pharmacokinetic implications of lorcainide therapy in patients with normal and depressed cardiac function.
The influence of cardiac function as measured by the left ventricular ejection fraction on the pharmacokinetic variables of a new antiarrhythmic drug, lorcainide, was investigated in 20 cardiac patients. Patients were divided into two groups: those with normal (ejection fraction greater than .40) or depressed (ejection fraction less than .40) left ventricular function. The elimination half-life, plasma clearance rates, or volume of distribution of lorcainide were not significantly different in patients with either normal or depressed cardiac function. A decrease in arrhythmia frequency could be correlated to plasma lorcainide concentration in the majority of patients, and it was noted that at least 0.1 mg/L of lorcainide was required for the presence of an antiarrhythmic effect. Three unusual cases are presented to illustrate the importance of measuring plasma drug concentrations and calculating the drug pharmacokinetics and to correlate these to the antiarrhythmic response in order to minimize the risk of plasma drug accumulation and side effects. A review of published data shows a three- to sixfold interpatient variation in the elimination half-life of lorcainide with practical implications in its use as an antiarrhythmic drug.
Somani
P
P
Department of Medicine, Medical College of Ohio, Toledo 43699.
Fraker
T D
TD
Temesy-Armos
P N
PN
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D044482:Benzeneacetamides; D005260:Female; D006331:Heart Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000889:Anti-Arrhythmia Agents; D044482:Benzeneacetamides; D010880:Piperidines; C015970:lorcainide