联苯双酯与环孢素合用对大鼠肝药物代谢酶的影响

Effect of Coadministration of Bifendate and Cydosporine on Liver Microsomal Drug Metabolizing Enzymes in Rats

目的:阐明联苯双酯与环孢素合用对药物代谢酶的影响。方法:采用分光光度法测定联苯双酯、环孢素及两者合用时大鼠肝微粒体红霉素N-脱甲基酶(erythromycin demethylabe,ERD)、氨基比林N-脱甲基酶(aminopyrence N-demethylabe,ADM)和谷胱甘肽S转移酶(glutathione S transferenase,GST)的含量或活性。结果:灌胃给药8 d,联苯双酯(200 mg·kg^(-1))对ADM和GST没有明显诱导作用。但对ERD有显著诱导作用(P<0.01);环孢素(20 mg·kg^(-1))对ERD和GST没有显著抑制作用(P<0.01);但对ADM有显著抑制作用;联苯双酯与环孢素合用对ADM和GST均有明显抑制作用(P<0.01)。结论:BFD是药物代谢酶ERD(CYP3A4)的诱导剂,是ADM(CYP1A1,2B1,2C11)的抑制剂;BFD与环孢素合用可以抑制ADM(CYP1A1、2B1、2C11)和GST的活性。

Objective： To study the effects of coadministration of bifendate（BFD） and cyclosporine A （CSA） on liver microsomal drug metabolizing enzymes in rats. Method： Liver microsomal erythromycin demethylase （ERD）, aminopyrence N-demethylase （ADM） and glutathiones S transferasnase（GST） activities were determined by spectrophotography. Result： BFD at 200 mg·kg^-l had no significant induction effects on ADM and GST, but it exhibited the induction actions on ERD in rats（P 〈0.01 ）. CsA at 20 mg·kg^-l could not markedly inhibit the activities of ERD and GST, but it could significantly inhibit the activities of ADM（P 〈 0.01 ）. ADM and GST were all inhibited by coadministration of BFD and CsA（P 〈0.01 ）. Condusion： BFD is an inductor of ERD（ CYP3A4）, but it is an inhibitor of ADM（ CYP1Al,2Bl,2Cll ） . The combination of BFD and CsA can inhibit activities of ADM（ CYP1A1,2B1,2Cll ）and GST.