Investigation of the pharmacokinetic behavior of barucainide in man during an early phase I study

The pharmacokinetic behavior of the class Ib antiarrhythmic drug barucainide was investigated in a phase I study in a group of 6 healthy male volunteers after oral administration of an initial single dose of 20 mg and incremental doses between 30 and 70 mg barucainide hydrochloride. After a lag time of about 1 h, median plasma concentration peaked at ca. 48 ng/ml barucainide hydrochloride 2.5 h after administration of 20 mg. The drug was finally distributed in a total volume of VB/f of about 630 l. With a terminal half-life of ca. 12.5 h (8-26 h) it was eliminated rather slowly. Elimination was predominantly due to metabolic processes; however, a median of 21% of the dose (7-28%) was recovered unchanged in the urine. Barucainide, in the dose range studied, was not subject to any appreciable first-pass effect; its metabolism apparently depended on the hydroxylation capacity of the volunteers. The doses administered were well tolerated. There were no changes in the cardiovascular parameters investigated, no adverse effects and no impairment of general well-being.