The phase I study of propafenone, a new antiarrhythmic agent.

A phase I study on propafenone hydrochloride (YM-13400), a new antiarrhythmic agent, was carried out in 12 healthy Japanese male volunteers . The safety, tolerance and pharmacokinetic profile of the drug were studied by single oral administration (group 1) and continuous administration (group 2). The six men of group 1 received 100, 200, and 300mg doses and the remaining six were given doses of 100 tid for 2 days, 200mg tid for 2days, and finally 200mg tid for 7days. Each dose were increased step by step at intervals of 2weeks or more after the safety of the drug was confirmed.No pronounced change was noted in vital signs (blood pressure, pulse rate), subjective symptoms, or clinical laboratory test data. Prolongation of PR, QRS and QTc interval was found at 2 to 4 hours after each administration.The maximum concentration (Cmax) and the area under the time-concentration curve (AUC) increased nonlinearly, increasing with each dosage. The biological half life in the elimination phase was about 2 to 3hours. In the continuous administration study, steady state was reached at about the 5 th day after administration. The amount of twenty-four hour cumulative urinary excretion of unchanged propafenone was 1% or less.The above results confirmed the safety of propafenone in healthy male volunteers.less.