The phase I trial of flecainide acetate, a new antiarrhythmic agent.

Safety, tolerance, and pharmacokinetics of flecainide acetate, a new antiarrythmic agent, were investigated by single blind study in 16 healthy Japanese volunteers. Each subject recieved a single oral dose (25, 50, 100, 150, 200, 250 mg, or placebo) and continuous oral dose (50, 100 mg b. i. d. or placebo for 7 days).No obvious change was observed in blood pressure, pulse rate, body temperature, clinical laboratory data, and subjective symptoms except only mild, transient side effects in some subjects.Prolongation of PQ and QRS interval was noted in proportion to the plasma concentration of the drug.The maixmum plasma concentration (Cmax) and the area under the time-concentrationcurve (AUC) were almost linear to oral doses. Cmax was attained in 1.5 to 2.5 hr and themean biological half-life in the elimination phase (t1/2β) was around 11 hr, independent ofdoses.The 24-hr cumulative urinary excretion of unchanged flecainide was around 30% and that of two major metabolites was detected to be around 15%.We concluded that these findings showed that oral flecainide acetate is well tolerated, has favorable pharmacokinetic properties, and can be expected to have clinical efficacy in patients with various cardiac arrythmias.