中文摘要：

目的：研究多次不同剂量PEG400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法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，以多次不同剂量PEG400处理组与阴性对照组的AU0.4h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（5mg·kg^-1，tid，3d）、PEG400（20mg·kg，tid，3d）分别增加咪哒唑仑AUC0-4h（1．9±0．5）（P〈0．05）、（1．14±0．21）倍，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±0．22）降至（0．27±0．11）和（0．58±0．14）（P〈0．05）。结论：2种剂量PEG400对CYP3A均有明显的抑制作用，PEG400（5mg·kg^-1，tid，3d）显著增加咪哒唑仑的生物利用度。

英文摘要：

OBJECTIVE To evaluate the effect of PEG400 on the activity of CYP3As in rat in vivo. METHODS Using midazolam as a probe, pharmacokinetics parameters for midazolam and its metabolite 1′-hydroxymidazolam were estimated from the plasma concentrations determined by HPLC. The ratio of 1′-OHMDZ/MDZ AUC0-4h was used to detect changes in CYP3A4 activity. RESULTS The pharmacokinetics parameters showed that multiple dose administration of PEG400 （5 mg·kg^-1, tid, 3 d）, PEG400 （20 mg·kg^-1, tid, 3 d） increased midazolam AUC0-4h 1.91-（P〈0. 05）, 1.14-fold, respectively, and significantly decreased the ratios of 1′-OH-MDZ/MDZ AUC0-4h from 1.09 ± 0. 22 to 0. 27 ± 0. 11 and 0. 58 ± 0. 14（P〈0. 05）, respectively. CONCLUSION This study indicates that two different doses of PEG400 with multiple administrations show significant inhibi tion on CYP3A. PEG 400 （5 mg·kg^-1, tid, 3 d） could increase the bioavailability of midazolam. Therefore, PEG 400 might be used to prepare drug formulations in pharmaceutical industry and would increase the bioavailability of some drugs transformed by CYP3As and further lead to significant clinical pharmacologic effect.