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Purpose of cytochrome P450 enzyme activity could be induced by many drugs or suppressed the drug itself or with a major change in the plasma concentration of other drugs, causing a common clinical drug interactions. Chinese medicine and more with the compound, the greater the possibility of such interactions. The purpose of this project is to establish suitable for rapid screening model for evaluation of traditional Chinese medicine CYP450 induced, to be commonly used in traditional Chinese medicine to be evaluated individually, hope the herbal compound compatibility reasonable to provide experimental basis. Different animals and different evaluation method to establish the experimental model, compare the feasibility and reliability as a screening model. (1) model I: rats before induction and after induction, all while giving the six kinds of CYP450 isoenzyme-specific probe drugs caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole ( CYP2C19), dextromethorphan dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4), intraperitoneal injection, using LC-MS/MS detection probe drug concentration in the whole blood at different time points, own comparison before induction and repeated after the induction of various probes AUC difference determine drug induced CYP450 isoenzymes, the model I evaluated dexamethasone the CYP450 isoenzyme activity induced; (2) model II: mice by inducing a few days later, while giving the CYP450 probe drugs: caffeine, tolbutamide, omeprazole, dextromethorphan, chlorzoxazone and midazolam alprazolam, and intraperitoneal injection the LC-MS/MS detection probe drug concentrations in whole blood at different time points, and the control group induced group the the various probes AUC changes determine drug induced CYP450 isoenzymes, and use the model II evaluation of dexamethasone, phenobarbital and rifampicin of of CYP450 isoenzyme activity induced; (3) the establishment of model III: mice by inducing a few days later, at the same time give the five kinds of the CYP450 probe drug: caffeine, tolbutamide, omeprazole, dextromethorphan and midazolam gavage using LC-MS/MS detection at different time points in the whole blood probe drugs and their metabolites (caffeine Vice xanthine tolbutamide 4 - hydroxy tolbutamide, omeprazole, and 5 - hydroxy-omeprazole, dextromethorphan right brown alkyl, midazolam and 1'-hydroxy microphone up alprazolam), concentration, and the control group, the various probes of the induction group metabolic rate (product concentration and the probe prototype concentration ratio) changes, determines the induction effect of the drug on CYP450 Isozymes, and evaluated with the model III dexamethasone and phenobarbital the of CYP450 isoenzyme activity induced; (4) rapid screening model III liquorice, schisandra, Angelica 46 flavor commonly used in clinical medicine, to examine these herbs with the work of the five major CYP450 enzyme (CYP1A2, 2C9, 2C19, 2D6 and 3A4) activity induced. Results (1) to establish a simultaneous detection of the six kinds of probe drugs in rat whole blood by LC-MS/MS analysis method, the high precision of the method, the recovery is good, meet the requirements for analysis of biological samples, can be used the combination probe Drugs Act. Dexamethasone-induced rat probe drug AUC and Cmax ratio induced a significant decrease showed that dexamethasone on CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 6 kinds of isozymes have induction. (2) establishing a simultaneous detection of the six kinds of probe drugs in mouse whole blood by LC-MS/MS analysis method, the high precision of the method, the recovery is good to meet the requirement of the analysis of the biological samples can be used for combination probe drugs The study of the Act. Compared with the control group of mice, the mice by ground dexamethasone induced 6 probe drug AUC and Cmax were decreased, showed that dexamethasone on CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 six kinds with isoenzymes are induced by; phenobarbital CYP1A2, 2D6, 3A4 inducing effect of CYP2C9, 2C19 and 2E1 had no obvious effect; rifampicin showed CYP1A2, 2C9, 2C19, 2D6 and 3A4 induction effect CYP2E1 no obvious role. (3) establish a LC-MS/MS analysis method for the simultaneous detection of five probe drugs in whole blood and its metabolites, the method is sensitive, accurate and good specificity, high precision can meet the biological samples analyzed requirements. Compared with the control group, the mice by dexamethasone-induced midazolam metabolic rate, the omeprazole metabolic rate and metabolic rate of tolbutamide significantly improve prompt dexamethasone on CYP2C9, 2C19 and 3A4 activity induced by. Phenobarbital-induced rate of caffeine metabolism, the midazolam metabolic rate, the rate of metabolism of omeprazole and tolbutamide metabolic rate significantly increased, indicating that the phenobarbital induced of CYP1A2 3A4, 2C19 and 2C9 activity. (4) From the rate of change of the probe drug metabolism, suggesting Angelica of CYP2C19, skullcap, of CYP2C19, licorice CYP3A4, turmeric CYP2C19, Schisandra capillaris of CYP3A4, CYP2C19, Ginkgo biloba on CYP2C9, Artemisia annua CYP2D6 and 3A4, Uncaria CYP2C9 and 3A4, Akebia CYP2D6, Eucommia CYP2C9, 2C19 and 3A4, Bupleurum of CYP2D6, 2C9 and 3A4, Atractylodes CYP2C9, Folium of CYP1A2 and 2C9, Alismataceae-2C19, dried tangerine peel on CYP1A2, Chuanwu of CYP3A4, aconite on CYP2C19 may induce. Ginkgo biloba CYP2C9, Artemisia annua on CYP2D6 and 3A4, Eucommia CYP2C9, 2C19 and 3A4, Bupleurum CYP2D6 and 3A4, Atractylodes CYP2C9 strong Folium role in the induction of CYP1A2. Salvia, forsythia, Evodia, Pueraria, Angelica, Chuanxiong, windproof, Breit, seaweed, Panax, berberine, astragalus, ephedra, Ophiopogon, Baiji, white peony root, honeysuckle, rhubarb, fritillary, Tianma, loquat, Guizhi the Anemarrhena, turmeric, Codonopsis, Campanulaceae, independent living, and Polygonum cuspidatum on CYP1A2, 2C9, 2C19, 2D6 and 3A4 activity without inducing effect. Conclusion combination of probe drugs as a whole animal model can be used for the rapid evaluation of chemical medicines or herbal on of CYP450 isoenzyme activity induced, particularly for the study of the interaction of this problem exist in Chinese herbal medicines ideas. After the study found to varying degrees in many traditional Chinese medicine to induce CYP450 activity, thus speeding up the metabolism of certain drugs in their own or their combination, reduce the efficacy of these drugs when used alone. In addition, the studies provide a theoretical basis and reference for the principle of compatibility of the rational use of traditional Chinese medicine and Chinese medicine.
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