Bae Jung-Woo, Choi Chang-Ik, Lee Hye-In, Lee Yun-Jeong, Jang Choon-Gon, Lee Seok-Yong
College of Pharmacy, Keimyung University, Daegu, Korea.
Int J Clin Pharmacol Ther. 2012 Sep;50(9):683-9. doi: 10.5414/CP201467.
The effects of CYP2C9*1/*3 and *1/*13 genotypes were evaluated on the pharmacokinetics of losartan and its active metabolite, E-3174, in Korean subjects.
Losartan (50 mg) was administered in 43 Korean volunteers with different CYP2C9 genotypes (CYP2C9*1/*1, *1/*3 and *1/*13). Losartan and E-3174 levels in the plasma and urine were analyzed by HPLC using fluorescence.
The CYP2C9*1/13 subjects showed lower oral clearance (p < 0.001) and greater AUC0-∞ (p < 0.01) of losartan and higher Cmax (p < 0.01) and longer half-life (p < 0.001) of E-3174 than the CYP2C91/1 subjects, but AUC0-∞ of E-3174 was not different. The CYP2C91/3 subjects showed lower oral clearance (p < 0.001) of losartan and higher Cmax (p < 0.01) and longer half-life (p < 0.01) of E-3174 than the CYP2C91/1 subjects. However, AUC0-∞ of losartan was greater in CYP2C91/3 subjects than in CYP2C91/1, but these results were not significant (p < 0.05, but statistical power < 0.8). In addition, AUC0-∞ of E-3174 was not different. There were no significant differences in pharmacokinetic parameters between the CYP2C91/13 and CYP2C91/*3 subjects.
These results suggest that CYP2C9*1/3 and CYP2C91/13 are similarly associated with decreased formation of E-3174 from losartan, but the clinical effects of losartan may not be reduced by CYP2C91/3 and CYP2C91/*13.
评估CYP2C9*1/3和1/*13基因型对韩国受试者中氯沙坦及其活性代谢产物E-3174药代动力学的影响。
对43名具有不同CYP2C9基因型（CYP2C9*1/*1、*1/3和1/*13）的韩国志愿者给予氯沙坦（50毫克）。采用荧光HPLC法分析血浆和尿液中氯沙坦和E-3174的水平。
与CYP2C9*1/1受试者相比，CYP2C91/13受试者的氯沙坦口服清除率较低（p<0.001），AUC0-∞较高（p<0.01），E-3174的Cmax较高（p<0.01）且半衰期较长（p<0.001），但E-3174的AUC0-∞无差异。与CYP2C91/1受试者相比，CYP2C91/3受试者的氯沙坦口服清除率较低（p<0.001），E-3174的Cmax较高（p<0.01）且半衰期较长（p<0.01）。然而，CYP2C91/3受试者中氯沙坦的AUC0-∞高于CYP2C91/1受试者，但这些结果无统计学意义（p<0.05，但检验效能<0.8）。此外，E-3174的AUC0-∞无差异。CYP2C91/13和CYP2C91/*3受试者之间的药代动力学参数无显著差异。
这些结果表明，CYP2C9*1/3和CYP2C91/13与氯沙坦生成E-3174减少的相关性相似，但CYP2C91/3和CYP2C91/*13可能不会降低氯沙坦的临床疗效。
