天然冰片对大鼠细胞色素P450四种亚型活性的影响

目的：用Cocktail探针药物法研究天然冰片对大鼠细胞色素P450四种亚型CYP1A2、CYP2C6/11、CYP2E1和CYP3A活性的影响。方法：将大鼠随机分为2组,给药组灌胃给予天然冰片-0.8%CMC-Na混悬液,剂量90mg/kg,对照组灌胃给予不含药物的0.8%CMC-Na溶液,每天1次,连续7d。于第8天,两组大鼠均尾静脉注射混合探针药物溶液（茶碱10mg/kg、甲苯磺丁脲2.5mg/kg、氯唑沙宗10mg/kg、氨苯砜5mg/kg）,眼内眦静脉采血,超高效液相色谱法检测各探针药物的血药浓度,采用WinNonlin 5.0.1计算药代动力学参数。结果：与对照组相比,天然冰片组中甲苯磺丁脲的t1/2、AUC0-t、AUC0-∞和MRT0-∞明显减小,两组之间的差异具有统计学意义（P〈0.05）;而两组之间茶碱、氯唑沙宗和氨苯砜的药代动力学参数则没有明显差异。结论：天然冰片对大鼠CYP2C6/11的活性具有诱导作用,对CYP1A2、CYP2E1和CYP3A活性无显著影响。

Effect of natural borneol on the activities of cytochrome p450 isoforms in rats

AIM： To study the effect of natu ral borneol on the activities of cytochrome P450enzymes CYP1A, CYP2C6/ll, CYP2E1 and CYP3A by a cocktail approach in rats. METH-ODS： The rats were randomly divided into two groups. One group of rats were treated with nat- ural borneol suspension containing 0.8% CMC- Na （90 mg/kg） by intragastric injection once a day for 7 days. At the same time, the rats in the other group received 0.8% CMC-Na solution serving as control group. On the 8th day, all rats in each group were intravenously injected with cocktail probe drugs （10 mg/kg theophylline, 2.5 mg/kg tolbutamide, 10 mg/kg chlorzoxa- zone, 5 mg/kg dapsone）. Blood samples were drawn into heparinized tubes at different time points. The plasma concentration of probe drugs were determined by ultra performance liquid chromatography （UPLC） and the main pharma-cokinetic parameters were calculated by Win- Nonlin 5. 0. 1. RESULTS： In natural borneol group, the tl/2, AUC0-t, AUC0-∞ and MRT0-∞ of tolbutamide were significantly lower than those in Control group （P〈0. 05）. There were no significant differences in the pharmaeokinetic parameters of theophylline, chlorzoxazone and dapsone between control group and natural bor- neol group. CONCLUSION. Natural borneol can induce the activity of CYP2C6/11, but has no influence on the activities of CYPIA2, CYP2E1 and CYP3A.