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.
Kang
W K
WK
Korea Institute of Toxicology, Yuseong-gu, Daejeon, Korea.
Yun
H-Y
HY
Kwon
K-I
KI
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D004095:Dihydropyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016568:Drugs, Generic / Q000008:administration & dosage / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D013607:Tablets; D013810:Therapeutic Equivalency
D004095:Dihydropyridines; D016568:Drugs, Generic; D013607:Tablets; C061004:benidipine