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纸质出版日期:2021,
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叶艮英, 何瑞荣, 梁淑贞, 等. 雷贝拉唑对不同CYP2C19基因型健康志愿者体内氯吡格雷及其活性代谢物药动学的影响[J]. 中国药房, 2021,32(5).
YE Genying, HE Ruirong, LIANG Shuzhen, et al. Effects of Rabeprazole on the Pharmacokinetics of Clopidogrel and Its Active Metabolite in Healthy Volunteers with Different CYP2C19 Genotypes[J]. China Pharmacy, 2021,32(5).
叶艮英, 何瑞荣, 梁淑贞, 等. 雷贝拉唑对不同CYP2C19基因型健康志愿者体内氯吡格雷及其活性代谢物药动学的影响[J]. 中国药房, 2021,32(5). DOI:
YE Genying, HE Ruirong, LIANG Shuzhen, et al. Effects of Rabeprazole on the Pharmacokinetics of Clopidogrel and Its Active Metabolite in Healthy Volunteers with Different CYP2C19 Genotypes[J]. China Pharmacy, 2021,32(5). DOI:
目的:探讨雷贝拉唑对不同CYP2C19代谢型健康志愿者体内氯吡格雷及其活性代谢物药动学特征的影响。方法:选择健康志愿者为对象,根据其CYP2C19基因型按随机数字表法挑选快代谢型、中间代谢型和慢代谢型受试者各8例分组,采用单剂量、随机、开放、两周期的交叉试验设计,各组患者在试验周期内分别单次口服硫酸氢氯吡格雷片300mg或硫酸氢氯吡格雷片300mg+雷贝拉唑钠肠溶片20mg,清洗期为7天。采用超高效液相色谱-串联质谱法检测受试者血浆中氯吡格雷及活性代谢产物H4(MP-H4)的质量浓度,通过DAS2.0软件计算药动学参数并比较。结果:3种代谢型受试者年龄、身高、体质量、肝酶、血肌酐等一般临床资料比较,差异均无统计学意义(P>0.05)。与单用氯吡格雷者比较,联用雷贝拉唑的快代谢型组受试者体内氯吡格雷的达峰浓度(cmax)和药-时曲线下面积(AUC0-)t分别上升了36%和27%,MP-H4的cmax和AUC0-t分别下降了34%和28%(P<0.01);中间代谢型受试者氯吡格雷的cmax和AUC0-t分别上升了19%和18%,MP-H4的cmax和AUC0-t分别下降了19%和16%(P<0.05或P<0.01);而慢代谢型受试者联用雷贝拉唑后体内氯吡格雷及MP-H4的cmax、AUC0-t以及各代谢型受试者体内氯吡格雷及MP-H4的tmax与单用氯吡格雷者比较,差异均无统计学意义(P>0.05)。结论:在CYP2C19快代谢型和中间代谢型受试者中,联用雷贝拉唑可明显增加氯吡格雷的暴露量并降低其活性代谢产物MP-H4的暴露量;而这种联用对CYP2C19慢代谢型受试者体内氯吡格雷及其活性代谢产物的影响并不显著。
OBJECTIVE:To investigate the effects of rabepr azole on the pharmacokinetic characteristics of clopidogrel and its active metabolite in healthy volunteers with different CYP2C19 genotypes. METHODS :Healthy volunteers were selected as subjects,and then randomly divided into extensive metabolizer (EM)group,intermediate metabolizer (IM)group,and poor metabolizer(PM)group with 8 subjects in each group ,according to their CYP2C19 genotypes by random number table. In single-dose,randomized,open,two-cycle-crossover design ,each group was given Clopidogrel bisulfate tablets 300 mg or Clopidogrel bisulfate tablets 300 mg+Rabeprazole sodium enteric-coated tablets 20 mg. UPLC-MS/MS method was adopted to detect the concentration of clopidogrel and its active metabolite derivative (MP-H4). The pharmacokinetic parameters were calculated and compared by DAS 2.0 software. RESULTS :There was no statistical significance in clinical data as age ,height, body weight ,liver enzymes and serum creatinine among 3 kinds of metabolism subjects (P>0.05). Compared with subjects receiving clopidogrel alone ,cmax and AUC 0-t of clopidogrel of subjects combined with rabeprazole in EM group were increased by 36% and 27%,while those of MP-H 4 were decreased by 34% and 28%(P<0.01);cmax and AUC 0-t of clopidogrel of subjects combined with rabeprazole in IM group were increased by 19% and 18%,while those of MP-H 4 were decreased by 19% and 16% (P<0.05 or P<0.01);there was no statistical significance in cmax and AUC 0-t of clopidogrel and MP-H 4 in PM group after receiving rabeprazole additionally as well as tmax of clopidogrel and MP-H 4 in all metablism subjects ,compared with clopidogrel alone(P>0.05). CONCLUSIONS :Among CYP2C19 EM and IM subjects ,combined use of rabeprazole can significantly increase the exposure of clopidogrel and decrease the exposure of its active metabolite MP-H 4,but has no significant impact on clopidogrel and its active metabolite in CYP2C19 PM subjects.
氯吡格雷活性代谢产物雷贝拉唑CYP2C19基因型药动学药物相互作用
ClopidogrelActive motaboliteRabeprazoleCYP2C19GenotypePharmacokineticsDrug interaction
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