STUDIES ON THE PHARMACOKINETIC PROFILE OF BARUCAINIDE IN MAN AFTER INTRAVENOUS, SINGLE ORAL AND MULTIPLE ORAL-ADMINISTRATION

The pharmacokinetic profile of barucainide was studied in a group of 4 healthy subjects after both short-term infusion and after single oral and multiple oral administration: 2 additional healthy subjects were exclusively given multiple oral doses. The dose levels used per subject were 20 mg by the intravenous and 70 mg by the oral route, as well as between 70-250 mg barucainide hydrochloride given repeatedly. The results obtained show that barucainide is absorbed relatively slowly after a short lag time of <0.5 h; from a relatively small central distribution volume of about about 43 l it is distributed rapidly (half-life about 4 min) into a total volume of 430 l. A total of about 90% is absorbed and there is only a minor first-pass metabolism (about 26%), so that an absolute bioavailability of about 66% results. With a terminal half-life of about 12 h, elimination is also relatively slow; accordingly, the mean total clearance of CL/f approx. 45 l/h is low. Renal clearance amounts to about 7.5 l/h and about 9-32% of the dose is recovered unchanged in the urine. Barucainide was well tolerated by all subjects. Impaired vision - ''blurred vision'' in 2 cases, ''narrowed field of vision'' in 1 case - were reported 1 h after administration only under the highest dosage at plasma concentrations of approx. 1000 ng/ml. This effect persisted for 1-2 h without impairing the general well-being of the 3 healthy subjects.