Study On The Effect Of Dai Medicine Decoction On The Activity Of Hepatic Drugs

ObjectiveThis topic adopt drug Cocktail probe method to study the effect of hepatic drug metabolizing enzyme subtype activity, explicit solution of the drug mechanisms of drug toxicity, and further reveal the characteristics of Dai medicine theory “Ya Jie(detoxification)” and Scientific Connotation of the antidote prescriptions, to guide clinical rational administration and provide experimental basis for national new drug research and development.Methods1、In Vivo expermentGet health rats 24, male and female in each half, according to the weight divided into 4 groups randomly, blank control group, positive drug group, drug level measurement group, Positive set of intragastric rats administration of phenobarbital 1.08mg/100 g, drug level measurement group give different concentration solution of “Ya Jie Sha Ba”. Equal volume of distilled water control group, Stomach volume for each group 1ml/100 g bw, 1day, 7 days in a row. After the last dose can not help but water for 18 hours of fasting, to probe Cocktail drugs solution. In urethane-anaesthetized rats after infection, respectively, in defferent time point underwent retinal venous blood collection,they are 10、30、50、70 min, 1. 5、2、2. 5、3、5、8、12h. Determinationoftheabove-mentionedprobedurginthebloodofrats(omeprazole,chlorzoxazone)con tent, calculation of drug metabolism parameters, evaluating the impact of “Ya Jie Sha Ba” on the CYP2C19、CYP2E1 metabolizing enzyme.2、In Vitro experimentThe group are the same as in vivo experiments, In the 18 hours after dosing water fasting can not help but kill, remove the liver of hepatic microsomal preparation. Omrua method by contrast, Sucrose and phosphate buffer solution suspension method hepatic microsomal protein content of the suspension prepared to determine the best method of hepatic microsomal preparation. Mixed enzymes in liver microsomes preparation of defferent PH values, incubation temperature, incubation time were investigated to determine the best liver microsomal enzyme incubation conditions. Probe in the determination of in vitro metabolism of drugs(caffeine, dapsone, omeprazole, chlorzoxazone) content, the pharmacokinetic parameters were calculated to evaluate“ Ya Jie Sha Ba ” drugs on the hepatic durg metabolizing enzyme CYP1A2, CYP3A4, CYP2C19,CYP2E1 impact.Result1、In Vivo expermentOmeprazole: after 7days continuous gavaging,“Ya Jie”high dose group(2.43 g pharmacognosy/kg) compared with blank control group, the CL/F of Omeprazole enhanced, the area under the curve(AUC)was significantly reduced,P<0.05; the half life(t1/2)compared with the blank control group, there is a decreasing trend, but the comparison among the groups, there was no significant difference(P>0.05).Chlorzoxazone: after 7days continuous gavaging, “ Ya Jie ” high dose group(2.43 g pharmacognosy/kg) and low dose group(0.27 g pharmacognosy /kg) compared with blank control group, the CL/F of Chlorzoxazone enhanced, the area under the curve(AUC)was significantly reduced, the half life(t1/2)shortening sensible, the difference was statistically significant(P<0.05 or P<0.01).2、In Vitro experimentCompared with the blank group, the chlorzoxazone content of“Ya Jie”high dose group(2.43 g pharmacognosy/kg) and low dose group(0.27 g pharmacognosy /kg) significantly reduced(P<0.01);dapsone and omeprazole concentration of“Ya Jie”high dose group significantly decreased(P<0.05),between the tow groups showed significant difference. “Ya Jie”high dose group and low dose group although there are trends for caffeine metabolism, but compared with the blank group, there was no significant difference(P>0.05).the results suggest that, “Ya Jie”can promote the dapsone, chlorzoxazone and omeprazole in vitro metabolism, may be it is CYP3A4、CYP2C19、CYP2E1’s enhancers.Conclusion“YaJieSha Ba” drug-induced effects on CYP450 subtype CYP3A4,CYP2C19,CYP2E1,can accelerate metabolism of drugs, improve gepatic drug metabolizing Enzyme Activity in an effort to enhance the role of solutions of drug toxicity.