Establishment of a rapid identification of adverse drug reaction program in R language implementation based on monitoring data / 浙江大学学报·医学版

OBJECTIVE@#To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use.@*METHODS@#Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r).@*RESULTS@#The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results.@*CONCLUSIONS@#In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.

Inhibitory effects of astragaloside IV on cytochrome P450 enzyme of rat liver microsomes / 中国中药杂志

<p><b>OBJECTIVE</b>To provide a scientific basis for the drug-combination and aim to examine whether astragaloside IV has the impact on the cytochrome P450 enzymes.</p><p><b>METHOD</b>Tolbutamide, chlorzoxazone, coumarin, nifedipine, and phenacetin were as probe substrates of rat CYP2C9, CYP2E1, CYP2A6, CYP3A4, and CYP1A2, and were incubated in rat liver microsomes with astragaloside IV. Triplicate samples were run to generate IC50 value by incubating P450 probe substrates in the presence of five concentrations of astragaloside IV in the incubation mixture. The K(i) values were determined by fitting the probe substrate at various inhibitor concentrations to the equations for competitive inhibition, noncompetitive inhibition, noncompetitive inhibition, and mixed-type inhibition.</p><p><b>RESULT</b>IC50 and K(i) values were estimated, and the types of inhibition were determined. Among the five probe substrates, astragaloside IV might not significantly affect CYP2E1, CYP2A6 and CYP1A2-mediated metabolism in rats, but was a competitive inhibitor of CYP2C9 (IC50 35.40 micromol x L(-1), K(i) 42.88 micromol x L(-1)), and was a uncompetitive inhibitor of CYP3A4 (IC50 88.24 micromol x L(-1), K(i) 33.31 micromol x L(-1)).</p><p><b>CONCLUSION</b>These results suggested that astragaloside IV inhibited CYP2C9 and CYP3A4, which provided useful information for safe and effective use of astragaloside IV.</p>