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The aim of the present study was designed to pharmacokinetic parameters by in vitro and in vivo methods to predict the series of compounds, the pharmacokinetic properties of the series of compounds for screening, in order to determine whether the compound early in the research and development continue to develop value for the series of compounds for further chemical modifications and pre-clinical studies provide a reference. After termination of the reaction of the method (1) of the series of compounds with SD rat liver microsomes metabolic stability screening, the reaction and incubated with 96-well plates, acetonitrile precipitated protein and the sample was centrifuged in 96-well plate processing method, a plurality of compound were combined LC -MS/MS detection means to obtain a series of compounds in vitro by liver microsomes metabolic the elimination half-life, clearance rate, and other information. (2) using the method of measuring time point sample mixed by LC-MS/MS determination of the compounds in SD rat plasma samples Y11, Y12, Y13, X01 concentration of compound for evaluation, Y11, Y12, Y13, X01 of the in vivo pharmacokinetics Properties of. (3) using rat liver microsomal incubation technology by chemical inhibitors inhibit the studied compounds y11 and y13 x01 metabolic phenotype. The results of the study completed the 35 compounds metabolic stability screening where compounds e26, b17, y13, y12, a16, c20, y11, b19, d22 eliminate the half-life of between 100-1400 min, compound f27 f29 y10 x02 Elimination half-life less than 10 min, the compound Y10, X02 may be provided with the protein in the microsome irreversible binding, almost undetectable, most of the compounds of the elimination half-life of 10-100 min; using SD the rat studies Y11, Y12, The y13, x01 absolute bioavailability, statistical moments processing lent bioavailability were 75.2%, 0.2%, 17.6%, 28.9%. Compound y11 and y13, x01 are multi-enzyme metabolism, CYP1A2 and CYP2A1 involved in compounds x01 metabolism, CYP1A2, CYP3A2 and CYP2A1 in the metabolism of compound y11 CYP1A2, CYP2C6, CYP2D1, CYP3A2, CYP2C11, CYP2A1 and CYP2E1 involved in the metabolism of the compounds y13 . Conclusion by high-throughput compound metabolic stability screening mode and sample hybrid approach, in vitro screening and in vivo screening effectively together to achieve the provincial effort, cost requirements; vitro metabolic phenotype can predict potential drug interactions. This study to achieve a high throughput of new drug pharmacokinetics, rapid screening purposes, and the preferred excellent pharmacokinetic properties of lead compounds will help to develop and reduce the risk of the development of new drugs.
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