抄録
The pharmacokinetics of cibenzoline, a new antiarrhythmic drug, were examined in healthy male volunteers. In a Latin Square, three-way crossover design, six subjects in three groups of two were given single 100-, 150-, or 200-mg oral doses of cibenzoline succinate in a fasting state.
The plasma and urinary concentrations of cibenzoline and its dehydro metabolite were determined by high performance liquid chromatography.
Cibenzoline plasma concentrations declined in a biexponential manner after reaching the maximum plasma concentrations. The mean±standard deviation maximum plasma concentrations of 201±39, 311±43, and 478±120 ng/ml were attained from 1 to 2 hours after doses of 100, 150, and 200 mg, respectively. The elimination half-life was dose-independent and averaged 5.47±0.59 hours. The maximum plasma concentration and the area under the plasma concentration-time curve increased in proportion to the dose. The maximum plasma concentrations of dehydro metabolite were very low and were about 1/20 times or less than those of cibenzoline. The average of 58.9±11.2 % of the given dose was excreted as cibenzoline dose-independently in the urine and only 1.13±0.55 % as dehydro metabolite.
Besides the above model-independent pharmacokinetic parameters, model-dependent parameters were also obtained by curve-fitting the plasma data to a two-compartment model with zero-order absorption.
Cibenzoline was well tolerated by all subjects. Clinically significant adverse effects were not observed.
