Bae Jung-Woo, Kim Ji-Hong, Choi Chang-Ik, Kim Mi-Jeong, Kim Hyung-Ji, Byun Seong-Ae, Chang Young-Soon, Jang Choon-Gon, Park Young-Seo, Lee Seok-Yong
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
Arch Pharm Res. 2009 Feb;32(2):269-73. doi: 10.1007/s12272-009-1232-z. Epub 2009 Mar 13.
The genetically polymorphic CYP2C9 metabolizes many non-steroidal anti-inflammatory agents, including naproxen. This study examined the effects of a CYP2C9 genetic polymorphism on the pharmacokinetics of naproxen in Korean subjects. Twenty healthy male subjects carrying a CYP2C9*1/1 (n=14) or CYP2C91/3 (n=6) polymorphism were enrolled. After a single-dose of 275 mg naproxen Na, blood samples were collected at various times over a 72 h period and the plasma naproxen concentration was measured. The plasma concentration of naproxen was determined by HPLC analysis with UV detection, and the pharmacokinetic parameters were calculated. The mean plasma concentration-time profiles of naproxen in the CYP2C91/3 and CYP2C91/1 individuals were similar. There were no significant differences in the pharmacokinetics of naproxen between CYP2C91/1 and CYP2C91/3 genotypes. The AUC(0-infinity) (p = 0.759) and oral clearance (p = 0.823) of naproxen were also similar in individuals with CYP2C91/3 and CYP2C91/1. Overall, a genetic polymorphism of CYP2C9 does not significantly affect the pharmacokinetics of naproxen. Therefore, naproxen does not require a dose adjustment for individuals with the CYP2C91/*3 genotype.
具有基因多态性的CYP2C9可代谢多种非甾体抗炎药，包括萘普生。本研究考察了CYP2C9基因多态性对韩国受试者中萘普生药代动力学的影响。招募了20名携带CYP2C9*1/1（n = 14）或CYP2C91/3（n = 6）多态性的健康男性受试者。单次服用275 mg萘普生钠后，在72小时内的不同时间采集血样，并测定血浆萘普生浓度。通过带紫外检测的高效液相色谱分析法测定萘普生的血浆浓度，并计算药代动力学参数。CYP2C91/3个体和CYP2C91/1个体中萘普生的平均血浆浓度-时间曲线相似。CYP2C91/1和CYP2C91/3基因型之间萘普生的药代动力学无显著差异。CYP2C91/3个体和CYP2C91/1个体中萘普生的AUC(0-∞)（p = 0.759）和口服清除率（p = 0.823）也相似。总体而言，CYP2C9的基因多态性不会显著影响萘普生的药代动力学。因此，对于CYP2C91/*3基因型个体，萘普生无需调整剂量。
