The pharmacokinetics and tissue distribution of the new antiarrhythmic agent lorcainide (R 15889) in rats.

After a single i.v. dose of 10 mg/kg the time course of 4'-chloro-N-(1-isopropyl-4-piperidyl)-2-phenyl-acetanilide (lorcainide, R 15889) concentrations in plasma, heart, lung, liver, kidney, spleen, brain, muscle and adipose tissue were followed for 10 h in rats. The new antiarrhythmic agent and a dealkylated metabolite were assayed by a specific gas liquid chromatographic procedure. Plasma level data were fitted by a digital computer program (SAAM 25) and analyzed according to the two-compartment open model. A rapid distribution phase with a T1/2(alpha) of 0.48 h was followed by the elimination phase with a T1/2(beta) of 3.3 h. Only minor amounts (less than 1% of the dose) of unchanged lorcainide could be recovered in urine and feces and total plasma clearance averaged 121.5 ml/min/kg. After 15 to 30 min maximal tissue concentrations could be observed, which were highest in spleen and lung (70--75) ng/mg). Only minor amounts could be measured in liver and adipose tissue (0.5--5 ng/mg). In heart, brain, kidney and muscle the maximal levels ranged between 17 and 35 ng/mg. Within 2 h the decline of these concentrations was very rapid and after 8 h lorcainide could be detected only in spleen, lung and adipose tissue.