目的：研究戊己丸不同配比方对大鼠体内CYP1A2 酶活性的影响，从药动学角度探讨戊己丸配伍机理，为临床优化给药提供借鉴。方法：以非那西丁为CYP1A2 酶活性研究探针药，HPLC 测定大鼠体内非那西丁及代谢产物——对乙酰氨基酚的血药浓度变化，间接反映CYP1A2 酶活性的大小；以正交法设计戊己丸3 因素3 水平交互的9 个实验点，考察所选取实验点对应的9 种戊己丸配比方对CYP1A2 酶活性的不同影响。结果：9 种戊己丸配比复方，组成戊己丸的黄连、吴茱萸、白芍3 单味药及对照组动物中，CYP1A2 酶活性从高到低依次为：8# 方、白芍、9# 方、7# 方、6# 方、1# 方、2# 方、4#方、对照组、3# 方、黄连、吴茱萸、5# 方；随着复方中黄连剂量水平的增大，酶活性呈增高趋势，复方中引入小、中剂量水平的吴茱萸或白芍可以增高CYP1A2 酶活性，但高剂量吴茱萸或白芍对CYP1A2 酶活性有抑制作用。结论：戊己丸各因素水平变化均可能对CYP1A2 酶活性造成影响，此种影响有可能是戊己丸药效学差异的原因之一；根据本实验结果可以优化戊己丸的临床应用。

Wuji Pills, a prescription of traditional Chinese medicine (TCM), are composed of Rhizoma Coptidis, Fructus Evodia Rutaecarpa and Radix Paeoniae Alba. This study aimed to investigate the effects of Wuji Pills with different compatibility on the levels of enzymatic activity of CYP1A2 in rat in vivo. The compatibility mechanism of Wuji Pills was also studied to confirm the relation between TCM compound prescription and its metabolism. This study also intended to make better scientific administration suggestions to the clinical application of Wuji Pills. Using phenacetin as a probe in vivo, levels of enzymatic activity of CYP1A2 were detected by high-performance liquid chromatography (HPLC). And the investigated drugs were 12 sorts of Wuji Pills, including 3 single herbs of Wuji Pills, 9 compound Wuji Pills with different ratio according to orthogonal design. The investigated drugs were marked from No.1 to No.9. The results showed that the administration of Wuji Pills significantly affected the process of probe and the metabolites in vivo in animals. From the high-level activity of CYP1A2 to the low-level, the sequence of the 12 sorts investigated drugs groups is: No.8, Radix Paeoniae Alba, No.9, No.7, No.6, No.1, No.2, No.4, control group, No.3, Rhizoma Coptidis, Fructus Evodia Rutaecarpa, and No.5. It was concluded that Wuji Pills with different compatibility, which have different pharmacodynamics and pharmacokinetics characteristics, are likely to be due to the different compatibility on CYP1A2. Conclusions made from this study can be used the scientific application of Wuji Pills.

国家自然科学基金重点课题基金资助项目（30930114）：基于药物相互作用的中药方剂配伍机理示范性研究，负责人：朱晓新；“重大新药创制”中药新药研发综合性大平台(2009ZX09301-005-009)：中药药代动力学平台建设，负责人：朱晓新；科学技术部国家“十一五”科技支撑计划项目（2006BAI08B04原4）：中医药诊疗与评价技术研究：中药复方作用和配伍评价研究———戊己丸示范性研究，负责人：朱晓新；国家中医药管理局中医药行业科研专项项目（2008070036）：基于药代动力学的金铃子散等两种中药复方配伍与效用关联性示范研究，负责人：梁日欣；中国中医科学院自主选题（ZZ20090212）：以微透析-膜片钳建立PK-PD 模型研究戊己丸药效的细胞机制，负责人：翁小刚。