Effect of gender and CYP2C9 and CYP2C8 polymorphisms on the pharmacokinetics of ibuprofen enantiomers

被引：30

作者：

Ochoa, Dolores ^{[1
]}

Prieto-Perez, Rocio ^{[1
]}

Roman, Manuel ^{[1
]}

Talegon, Maria ^{[1
]}

Rivas, Angela ^{[1
]}

Galicia, Ignacio ^{[2
]}

Abad-Santos, Francisco ^{[1
,3
]}

Cabaleiro, Teresa ^{[1
,3
]}

机构：

[1] Hosp Univ Princesa, Clin Pharmacol Serv, Inst Teofilo Hernando, Inst Invest Sanitaria Princesa IP, Madrid 28006, Spain

[2] Fdn Teofilo Hernando, Madrid 28049, Spain

[3] Inst Salud Carlos III, CIBERehd, Madrid 28029, Spain

来源：

PHARMACOGENOMICS | 2015年 / 16卷 / 09期

关键词：

CYP2C8; CYP2C9; ibuprofen; pharmacokinetics; polymorphisms; CYTOCHROME P4502C9 POLYMORPHISMS; IN-VITRO; FUNCTIONAL-CHARACTERIZATION; HEALTHY-VOLUNTEERS; METABOLISM; PHARMACODYNAMICS; GENOTYPES; ACID; (R)-IBUPROFEN; VARIABILITY;

D O I：

10.2217/pgs.15.40

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aim: To evaluate the effect of polymorphisms in CYP2C9 and CYP2C8 and gender on the pharmacokinetics of the enantiomeric forms of ibuprofen. Materials & methods: 122 healthy volunteers were genotyped for polymorphisms in CY2C8 and CYP2C9 using real-time PCR. Results:CYP2C8 polymorphisms affected neither R- nor S-ibuprofen. CYP2C9*3 and CYP2C9*2 carriers had a lower S-ibuprofen clearance and a higher S-ibuprofen AUC and half-life. R-ibuprofen clearance was decreased in CYP2C9*3 carriers. Gender affected R-ibuprofen and S-ibuprofen pharmacokinetics. Multiple regression analysis showed that CYP2C9*2, CYP2C9*3 and gender were associated with S-ibuprofen clearance, but only CYP2C9*3 was associated with R-ibuprofen clearance. Conclusion: The pharmacokinetics of S-ibuprofen and R-ibuprofen is affected by CYP2C9 polymorphisms and gender. CYP2C8 polymorphisms do not have a significant role. Original submitted 6 February 2015; Revision submitted 1 April 2015

引用

页码：939 / 948

页数：10

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