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目的研究单次不同剂量聚乙二醇(PEG)400对大鼠体内细胞色素P4503A活性的影响。方法以咪哒唑仑为探针,HPLC测定咪哒唑仑及其代谢物1′-羟基咪哒唑仑在大鼠体内的血药浓度并计算其药动学参数,以不同剂量PEG400处理组与阴性对照组的AUC0-4h比值为指标,研究它们对大鼠体内细胞色素P4503A药酶活性的影响。结果与生理盐水组相比,PEG400(15mg·kg-1)、PEG400(60mg·kg-1)分别显著增加咪哒唑仑AUC0-4h1.98,1.75倍(P<0.05),显著降低1′-羟基咪哒唑仑与咪哒唑仑AUC0-4h的比值,分别从1.09降至0.26和0.28(P<0.05)。结论两种剂量PEG400对CYP3A均有明显的抑制作用。
Objective To investigate the effect of single dose of polyethylene glycol (PEG) 400 on the activity of cytochrome P4503A in rats. Methods Using midazolam as a probe, the plasma concentration of midazolam and its metabolite 1’-hydroxymidazolam in rats was determined by HPLC and its pharmacokinetic parameters were calculated. With different doses of PEG400 treatment group And negative control group AUC0-4h ratio as an index to study their effects on cytochrome P4503A drug activity in rats. Results Compared with the saline group, PEG400 (15 mg · kg -1) and PEG400 (60 mg · kg -1) significantly increased the midazolam AUC0-4h1.98,1.75 fold (P <0.05) and significantly decreased the 1 ’ - The ratios of hydroxymidazolam to midazolam AUC0-4h decreased from 1.09 to 0.26 and 0.28, respectively (P <0.05). Conclusion Both doses of PEG400 have obvious inhibitory effect on CYP3A.