CYP2C9*3/*3 个体中，美洛昔康的暴露量显著增加。
Strongly increased exposure of meloxicam in CYP2C9*3/*3 individuals.
机构信息
aDepartment of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon bDepartment of Pharmacology, College of Pharmacy, Keimyung University, Daegu cDepartment of Pharmacotherapy, College of Pharmacy, Dankook University, Cheonan, Republic of Korea.
出版信息
Pharmacogenet Genomics. 2014 Feb;24(2):113-7. doi: 10.1097/FPC.0000000000000025.
OBJECTIVE
The effects of CYP2C9*1/*3 and *3/*3 genotypes on the pharmacokinetics and pharmacodynamics of meloxicam were evaluated in healthy Korean subjects.
METHODS
After oral administration of 15 mg meloxicam, the plasma concentrations of meloxicam were assessed in 11 CYP2C9*1/1 individuals, eight CYP2C91/3 individuals, and three CYP2C93/*3 individuals. The pharmacodynamic effects were determined by measuring thromboxane B2 generated in blood.
RESULTS
A nine-fold lower apparent oral clearance and an eight-fold higher AUC0-∞ of single-dose meloxicam were observed in CYP2C9*3/3 individuals when compared with CYP2C91/1 individuals. CYP2C93/*3 individuals also showed markedly increased inhibition of thromboxane B2 generation by meloxicam.
CONCLUSION
These results indicate that CYP2C9*3/*3 individuals may be at a higher risk for concentration-dependent adverse effects during long-term treatment with standard doses of meloxicam.
目的
评估 CYP2C9*1/*3 和 *3/*3 基因型对健康韩国受试者体内美洛昔康药代动力学和药效学的影响。
方法
在 11 名 CYP2C9*1/1 个体、8 名 CYP2C91/3 个体和 3 名 CYP2C93/*3 个体中，口服给予 15mg 美洛昔康后，评估美洛昔康的血浆浓度。通过测定血液中生成的血栓素 B2 来确定药效学效应。
结果
与 CYP2C9*1/1 个体相比，CYP2C93/3 个体单次给予美洛昔康后的表观口服清除率低 9 倍，AUC0-∞高 8 倍。CYP2C93/*3 个体还表现出美洛昔康对血栓素 B2 生成的抑制作用明显增加。
结论
这些结果表明，CYP2C9*3/*3 个体在长期接受标准剂量美洛昔康治疗时，可能存在更高的与浓度相关的不良反应风险。
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