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

Summary 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 × 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 (AUC t ) was calculated using the linear‐log trapezoidal rule. The maximum plasma drug concentration ( C max ) and the time to reach C max ( T max ) were compiled from the plasma concentration–time data. Analysis of variance was carried out using logarithmically transformed AUC t and C max , and untransformed T max . Results:  The geometric mean AUC t was 2·23ng/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 C max 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 AUC t and C max 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.