厄贝沙坦、氯沙坦对兔体内环孢素A药动学的影响

Effect of Irbesartan and Losartan on Pharmacokinetics of Cyclosporin A in Rabbits

目的:研究厄贝沙坦、氯沙坦对家兔体内环孢素A(CsA)药动学的影响。方法:12只家兔随机分成2组,每组6只。每组采用自身对照法,分别测定合用厄贝沙坦、氯沙坦前、后CsA的血药浓度,并对主要药动学参数进行比较。结果:与合用前比较,合用厄贝沙坦、氯沙坦后CsA的Cmax均显著升高(P<0.01),AUC0～24均显著增加(P<0.01),血浆清除率、表观分布容积均显著降低(P<0.05或P<0.01),其余药动学参数无显著性变化。结论:合用厄贝沙坦、氯沙坦后可升高CsA的血药浓度,临床上其与CsA合用需监测CsA的血药浓度,以保证治疗的安全有效。

OBJECTIVE： To study the effect of irbesartan and losartan on pharmacokinetics of cyclosporin A （CsA） in rabbits. METHODS： 12 rabbits were randomly divided into two groups （n=6）. In self-controlled study, plasma concentration of CsA in rabbits of two groups before and after treating with combination of irbesartan and losartan were determined and pharmacokinetics parameters were examined. RESULTS： After combination of irbesartan or losartan, the Cmax and AUC0-24 of CsA were significantly increased （P〈0.01）, plasma clearance （CL） and apparent volume of distribution （Vd） significantly decreased （P〈0.05 or P〈 0.01）. The remaining pharmacokinetic parameters had no significant changes. CONCLUSION： lrbesartan and losartan can increase blood concentrations of CsA and the combination use of the two drugs in clinic requires monitoring CsA blood concentration to ensure safe and effective treatment.