Prediction of human in vivo hepatic clearance from in vitro experiments in humans and rats and molecular descriptors of drugs = 인간과 쥐의 세포실험과 약물의 분자표현자를 이용한 간에서의 약물소실 예측

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Hepatic clearance is one of the most important pharmacokinetic parameters that affect ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) of drugs in human body, explaining metabolism and elimination steps among ADMET processes. The present study demonstrated that the information of molecular descriptors of drugs helps to increase the accuracy of prediction of human in vivo hepatic clearance from in vitro experimental data in humans and ats. Predictions were made for two datasets obtained from in vitro hepatocyte assay and in vitro microsome assay. I proposed a new method that combines experimental data and information of molecular descriptors of drugs. The prediction error and correlation between the predicted and observed values of the new method were compared with those of previous methods (methods using scaling factor, drug-specific scaling factor, and multiple linear regression analysis, respectively) that use experimental data only. Results showed that the new method was the most accurate prediction model with the lowest prediction errors and the strongest correlations for both datasets. In addition, the present study showed that (1) in vitro experimental data in humans and rats are important for predicting human in vivo hepatic clearance, (2) rat in vivo data are not essential for prediction, (3) the molecular descriptors are very useful to improve prediction accuracy, and (4) in vitro data in hepatocyte experiments are more useful than in microsome experiments. These results suggest that the information content of molecular descriptors is significant for the prediction of human in vivo pharmacokinetic parameter from in vitro experimental data. Since the present approach does not use in vivo animal data, application of the new method is most appropriate for predicting human pharmacokinetic parameters such as hepatic clearance by high-throughput. Prediction from only in vitro experimental data cuts down expenses and the time. The...
Advisors
Kim, Dong-supresearcher김동섭researcher
Description
한국과학기술원 : 바이오시스템학과,
Publisher
한국과학기술원
Issue Date
2006
Identifier
301298/325007  / 020043405
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 바이오시스템학과, 2006.2, [ vi, 31 p. ]

Keywords

human hepatic clearance; in vitro; molecular descriptor; prediction; 간 클리어런스; 시험관내 실험 데이터; 분자표현자; 예측; human hepatic clearance; in vitro; molecular descriptor; prediction; 간 클리어런스; 시험관내 실험 데이터; 분자표현자; 예측

URI
http://hdl.handle.net/10203/27157
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=301298&flag=dissertation
Appears in Collection
BiS-Theses_Master(석사논문)
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