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- Title
Drug-drug interaction of rabeprazole and clopidogrel in healthy Chinese volunteers.
- Authors
Wu, Jia; Jia, Li-Tao; Shao, Li-Ming; Chen, Jia-Min; Zhong, Dan-Dan; Xu, Song; Cai, Jian-Ting
- Abstract
Purpose: This study was aimed to determine the impact of rabeprazole (RBRZ) on the antiplatelet efficacy of clopidogrel (CPG) in healthy Chinese volunteers, and further to predict the effect of CYP2C19 genetic polymorphism on the efficacy of rabeprazole and clopidogrel. Methods: The open-label, two period cross-over study was conducted in 20 healthy Chinese subjects with different CYP2C19 genotypes receiving clopidogrel, rabeprazole or the two drugs, respectively. All the volunteers were divided into two groups, poor metabolizers (PMs) and extensive metabolizers (EMs), depending on CYP2C19 genotypes. Blood samples were collected at baseline and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 h after administration. The plasma concentrations of rabeprazole and clopidogrel were analyzed by LC-MS/MS and ADP-induced platelet aggregation was detected by the optical turbidimetric method. Results: There were no significant differences in the mean plasma concentration-time curves of clopidogrel (CPG), the inactive metabolite clopidogrel carboxylic acid (CPG-CA), the active metabolite clopidogrel-MP-Derivative (MP-AM), and rabeprazole (RBRZ) according to the co-administration of CPG and RBRZ. There were no major changes in the pharmacokinetics of CPG and RBRZ. The maximal ADP-induced platelet aggregation (2 μmol/L) was decreased in EMs compared with PMs. Conclusion: Co-administration of rabeprazol and clopidogrel did not affect the antiplatelet efficacy of clopidogrel. The CYP2C19 genetic polymorphism may impact the efficacy of clopidogrel.
- Subjects
CHINA; MASS spectrometry methodology; LIQUID chromatography; ACADEMIC medical centers; BIOLOGICAL assay; CROSSOVER trials; DRUG interactions; GENES; GENETIC polymorphisms; STATISTICS; T-test (Statistics); PROTON pump inhibitors; DATA analysis; CLOPIDOGREL; PLATELET aggregation inhibitors; DESCRIPTIVE statistics; PHARMACODYNAMICS
- Publication
European Journal of Clinical Pharmacology, 2013, Vol 69, Issue 2, p179
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-012-1329-z