生物学的同等性とバイオアベイラビリティのジャーナル

概要

Bioequivalence Study of Clopidogrel 75 Mg Tablets in Healthy Male Volunteers

Jian-Jun Zou, Jie Tan, Hong-Wei Fan and Shao-Liang Chen

The marked inter-individual and ethnic variabilities in the metabolism of clopidogrel has been investigated. Although the pharmacokinetics (PK) of clopidogrel has been reported previously in Whites and Korean volunteers, the PK characteristics may not be fully extrapolated to the Chinese population. Little is known about the PK characteristics and relative bioavailability of clopidogrel in Chinese population. The present study was to assess the PK characteristics and relative bioavailability of clopidogrel in healthy Chinese volunteers. A single-dose, randomized-sequence, open-label, 2-period crossover study was performed in fasting healthy Chinese male volunteers. Eligible subjects were randomly assigned to receive a single 75-mg dose of the test or reference formulation of clopidogrel, followed by a 1-week washout period and administration of the alternate formulation. The plasma samples were collected and at 0 min (baseline), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 11, 14, 24 and 36 hours, respectively, after drug administration. The concentrations of both clopidogrel and SR26334 were detected by a validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS). The formulations were considered to be bioequivalent if the 90% CIs for the log-transformed values were within the predetermined equivalence range (80%–125% for AUC and C_max). For clopidogrel, the 90% CIs for the log-transformed ratios of C_max and AUC_0–t were 90.26%–113.91% and 91.82%–103.27%, respectively. For SR26334, the 90% CIs were 85.23%–112.97% and 93.11%–103.67%, respectively. In conclusion, the present results show that the formulation of clopidogrel was of bioequivalence to the reference, which have been tested in fasting, healthy, male Chinese volunteers.