Prediction of drug-drug interaction coused by xenobiotic metabolizing enzymes.

以覆盆子酮的香气成分圣约翰草1000mg/kg/d给药Wistar大鼠，连续7 d。在最后一次给药圣约翰草24小时后，以10mg/kg的剂量口服咪达唑仑（一种检测CYP3A活性的底物）。采用与模型无关的方法评价咪达唑仑的药代动力学。在圣约翰草开始给药后3天和7天，咪达唑仑的总清除率显著增加。圣约翰草处理后大鼠肝微粒体咪达唑仑代谢活性显著高于对照组，表明圣约翰草诱导了CYP3A。另一方面，覆盆子酮制剂不影响咪达唑仑的全身清除率或CYP3A活性。

St.John's wort, an aroma component of raspberry ketone, was administered to Wistar rats at the dose of 1000mg/kg/day for 7 days. At 24hr after final administration of St.John's wort, midazoram, an probe substrate for CYP3A activity, was orally administered at the dose of 10mg/kg. Pharmacokinetics of midazoram was evaluated using model-independent method. Total body clearance of midazoram was significantly increased at 3 days and 7 days after the start of St.John's wort administration. The activity of midazoram metabolism in liver microsome after St.John's wort treatment was significantly higher than that in control rats, indicating CYP3A induction by St.John's wort. On the other hand, raspberry ketone preparations did not affect the total body clearance of midazoram or CYP3A activity.