Disposition and antiarrhythmic effect of lorcainide.
The disposition and the antiarrhythmic effect of lorcainide (R 15,889) were investigated in 11 patients with ventricular premature beats (VPB) after a single intravenous dose of 100 mg or 2 mg/kg and after multiple intravenous and oral dosing. Pharmacokinetic parameters were computed according to the two-compartment open model. The half-life of the initial phase, t 1/2 (alpha), was calculated as 0.3 +/- 0.1 hr (mean +/- SD) and the terminal half-life, t 1/2 (beta), varied independently of the dose and route of administration between 5.8 and 12.5 hr (7.8 +/- 2.5 hr). After the single intravenous dose total plasma clearance (Cl) ranged from 570 to 1670 ml/min (988 +/- 425 ml/min) while after multiple dosing Cl decreased to 666 +/- 27 ml/min. Comparison of the area under the curves during steady state (ss) indicated a complete bioavailability of multiple oral doses. After the single intravenous dose, VPB were diminished or reduced for about 4 hr if the plasma concentrations exceeded 120 to 150 ng/ml. During ss-therapy plasma levels fluctuated between 200 and 550 ng/ml with an effective prevention of arrhythmias. Thus, the new drug demonstrates a therapeutic range of approximately 150 to 400 ng/ml and oral therapy seems to be effective with 100 mg t. i. d.
D000083:Acetanilides / Q000378:metabolism / Q000627:therapeutic use; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000378:metabolism* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D044482:Benzeneacetamides; D002986:Clinical Trials as Topic; D003640:Dealkylation; D004562:Electrocardiography; D005260:Female; D006207:Half-Life; D006352:Heart Ventricles; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000378:metabolism* / Q000627:therapeutic use
D000083:Acetanilides; D000889:Anti-Arrhythmia Agents; D044482:Benzeneacetamides; D010880:Piperidines; C015970:lorcainide