Assessing the bioequivalence of 4- and 8-mg benidipine tablets in healthy volunteers after a single oral dose.

OBJECTIVE

To assess the bioequivalence of a new tablet formulation of benidipine hydrochloride with reference to a marketed product.

METHODS

Two groups, consisting of 24 healthy volunteers each, received a 4- or 8-mg (one or two tablets) reference benidipine hydrochloride tablet and one or two test tablets in a 2 x 2 cross-over study. There was a 6-day washout period between doses. The plasma benidipine concentration was monitored using LC/MS/MS for 8 h after the dose. The area under the plasma concentration-time curve from time 0 to the last sampling time (AUCt) was calculated using the linear-log trapezoidal rule. The maximum plasma drug concentration (Cmax) and the time to reach Cmax (Tmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUCt and Cmax, and untransformed Tmax.

RESULTS

The geometric mean AUCt was 2.23 ng/mL/h (test medication) and 2.47 ng/mL/h (reference medication) for the 4-mg tablet, and 9.57 and 9.97 ng/mL/h for the 8-mg tablet, respectively. A Cmax of 1.94 and 2.01 ng/mL was achieved for the test and reference medication for the 4-mg tablet, and 5.94 and 6.53 ng/mL for the 8-mg tablet, respectively. The 90% confidence intervals for AUCt and Cmax were 0.8441-1.0481 and 0.8739-1.2037 for the 4-mg tablet, and 0.8559-1.1273 and 0.9926-1.2176 for the 8-mg tablet, respectively, satisfying the bioequivalence criteria of the US Food and Drug Administration Guidelines, and the Korea Food and Drug Administration Guidelines. These results indicate that the 4- and 8-mg tablets of benidipine are bioequivalent to the reference formulations.