氯苯氧异丁酸甲氧基苯丙烯酸酯代谢物在大鼠体内的药动学

Pharmacokinetics of the active metabolite chlorophenoxy isobutyric acid in rat plasma after oral administration of a new compound AZ at different dosages

目的:研究不同剂量氯苯氧异丁酸甲氧基苯丙烯酸酯{(E)-3-[4-[2-(4-chlorophenoxy)-2-methylpropanoyloxy]-3-me-thoxyphenyl]acrylic acid,AZ}灌胃给药后活性代谢产物氯苯氧异丁酸在大鼠体内药动学。方法:3组大鼠按体质量分别灌胃给予125,250,500 mg.kg-1的AZ后,以布洛芬为内标物,采用高效液相色谱法测定代谢产物氯苯氧异丁酸的血药浓度,各组结果分别用DAS 2.0软件进行药动学分析,组间药动学参数用SPSS11.5软件进行统计分析。结果:低、中剂量组氯苯氧异丁酸的t1/2,CL/F,MRT均无显著性差异,AUC随给药剂量增加线性增大。高剂量组与中剂量相比,t1/2变大,CL/F显著减小,MRT显著延长。结论:口服AZ在125～250 mg.kg-1剂量时,其代谢产物氯苯氧异丁酸在大鼠体内符合线性动力学过程,剂量在500 mg.kg-1以上时则表现为非线性动力学特征。

OBJECTIVE To study the pharmacokinetics of chlorophenoxy isobutyric acid in rats after the treatment of differ ent doses of AZ { （E）-3-[4-（4-chlorophenoxy）-2 methylpropanoyloxy]-3 methoxyphenyl] acrylic acid} by oral administra tion. METHODS After three groups of rats were given AZ in a single oral dose of 125,250, 500 mg·kg^-1 by weight separately, the concentrations of chlorophenoxy isobutyric acid in plasma were determined by HPLC. The mean plasma concentration time curves of different medication administration teams were processed with DAS 2. 0 pharmacokinetic software. The pharmacoki netic parameters of chlorophenoxy isobutyric acid at different dosages were analyzed with SPSS 11.5 software. RESULTS t1/2, CL/F,MRT was no significant difference,and AUC was linear increase between low and middle dosage group. Meanwhile,t1/2 was increased,CL/F was significantly decreased and MRT was significantly prolonged between high dosage group and middle dosage group. CONCLUSION The results indicated that the pharmacokinetics of chlorophenoxy isobutyric acid were fitted to linear pharmacokinetics by oral administration of AZ at dosage range of 125-250 mg·kg^-1 ,and nonlinear pharmaeokinetics at the dosage more than 500 mg·kg^-1.