Effect of rabeprazole on steady-state pharmacokinetics of clopidogrel in rats
- Author:
Wei-Ming WU
1
Author Information
- Publication Type:Journal Article
- Keywords: Clopidogrel; Drug-interaction; Omeprazole; Pharmacokinetics; Rabeprazol; SR26334
- From: Chinese Pharmaceutical Journal 2013;48(4):289-292
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To study the effect of rabeprazole on the steady-state pharmacokinetics of clopidogrel in rats. METHODS: Eighteen healthy SD rats were divided into three groups, which were intragastricly administered clopidogrel (30 mg · kg-1 middot; d-1), rabeprazole (8 mg · kg-1 middot; d-1) + clopidogrel (30 mg · kg-1 middot; d-1), omeprazole (8 mg · kg-1middot; d-1) + clopidogrel (30 mg · kg-1 middot; d-1) respectively for 7 d. The plasma concentrations of the metabolite of clopidogrel, SR26334, were determined by HPLC-DAD. The pharmacokinetic parameters of SR26334 were obtained with statistical analysis by DAS 3.0. RESULTS: There was no significant difference between the single-drug group and the rabeprazole combination group in the main pharmacokinetic parameters of SR26334, such as AUC0-t, AUC0-∞, MRT0-t, t1/2, CLz/F, ρmax and ρss (P≤0.05), except that the tmax significantly decreased from (1.17±0.41) h in the single-drug group to (0.58±0.20) h in the combination group (P<0.01). Compared with single-drug group, the AUC0-t, and AUC0-∞ of the omeprazole combination group increased for about 20% (P<0.05), MRT0-t significantly prolonged (P<0.01), and CLz/F decreased for about 20% (P<0.05). CONCLUSION: Long-term combinaton treatment with rabeprazole can accelerate the in vivo metabolism of clopidogrel to SR26334, but there is no significant influence on the degree of metabolism.
