目的 用“cocktail”探针药物法研究单次或多次口服辣椒素对大鼠肝药酶CYP1A2、CYP2C11和CYP3A的影响。方法 将雄性SD大鼠随机分组，给予辣椒素25 mg·kg-1，分别灌胃1, 3, 7 d，以0.5%羧甲基纤维素钠作为空白对照组，每组8只，给药后于不同的时间点采集血样。用HPLC测定大鼠血浆中探针药物咖啡因、甲苯磺丁脲和氨苯砜的浓度，血药浓度-时间数据采用DAS2.1.1软件进行药动学分析。结果 与对照组相比，辣椒素灌胃7 d后，咖啡因的AUC0-t、AUC0-∞和ρmax显著减小, CL/F显著增大；甲苯磺丁脲的AUC0-t显著减小，ρmax极显著减小；氨苯砜的AUC0-t和AUC0-∞极显著减小，CL/F和V/F极显著增大。结论 辣椒素灌胃7 d后对大鼠肝药酶CYP1A2、CYP2C11和CYP3A可能存在不同程度的诱导作用，其中对CYP3A的诱导作用较强。
Abstract
OBJECTIVE To study the effect of capsaicin on the activities of CYP1A2, 2C11 and 3A in rats by cocktail probe drug method. METHODS Male rats were randomly divided into six groups. Three groups of rats (group A, B and C) were orally given capsaicin 25 mg·kg-1 once daily for 1, 3, 7 d, respectively. The other three groups (group a, b and c) received orally 0.5% carboxymethylcellulose sodium (CMC-Na) once daily for 1, 3, 7 d, respectively, as the blank control groups. Plasma was collected at different time after drug administration. The concentrations of caffeine, tolbutamide and dapsone in plasma were determined by HPLC method. The plasma concentration-time data was analyzed with DAS2.1.1 software to obtain the pharmacokinetic parameters of the cocktail probe drugs. RESULTS Compared with the blank control group, the AUC0-t, AUC0-∞ and ρmax of caffeine in group C significantly decreased, along with significant increase of CL/F. The AUC0-t and ρmax of tolbutamide in group C both significantly decreased compared with the blank control group. Meanwhile, the AUC0-t and AUC0-∞ of dapsone in group C significantly decreased, along with significant increase of CL/F and V/F. CONCLUSION Capsaicin may significantly induce the activities of CYP1A2, CYP2C11 and CYP3A in rats after consecutive administration for 7 d. Reduced therapeutic efficacy of the drugs metabolized by CYP1A2, CYP2C11 and CYP3A should be anticipated during long-term administration of capsaicin.
关键词
cocktail /
CYP450 /
辣椒素 /
咖啡因 /
甲苯磺丁脲 /
氨苯砜 /
探针药物
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Key words
cocktail /
CYP450 /
capsaicin /
caffeine /
tolbutamide /
dapsone /
probe drug
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中图分类号：
R965
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