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The present study demonstrated that the information of molecular descriptors of drugs increases the accuracy of predicting human in vivo hepatic clearance from in vitro experimental data in humans and rats. A new method uses not only the experimental data but also the information of molecular descriptors. Predictions for the datasets from hepatocyte experiments and microsome experiments were made by the present method, and the prediction accuracy was compared with those of the previous methods, such as methods using in vitro-in vivo scaling factor and multiple linear regression analysis, that use only the experimental data. Results showed that the present method was the most accurate prediction model with the lowest prediction errors and the strongest correlations. These results suggest that the information of molecular descriptors is significant for predicting the human in vivo pharmacokinetic parameters from in vitro experimental data. This study also demonstrated that in vitro experimental data in humans and rats were important information for predicting human in vivo hepatic clearance, and the additional rat in vivo data were not significant for prediction with the information of molecular descriptors. These results imply that the present method can be useful for highthroughput drug candidate screening by reducing the time and cost in the early stage of the drug discovery process.


The present study demonstrated that the information of molecular descriptors of drugs increases the accuracy of predicting human in vivo hepatic clearance from in vitro experimental data in humans and rats. A new method uses not only the experimental data but also the information of molecular descriptors. Predictions for the datasets from hepatocyte experiments and microsome experiments were made by the present method, and the prediction accuracy was compared with those of the previous methods, such as methods using in vitro-in vivo scaling factor and multiple linear regression analysis, that use only the experimental data. Results showed that the present method was the most accurate prediction model with the lowest prediction errors and the strongest correlations. These results suggest that the information of molecular descriptors is significant for predicting the human in vivo pharmacokinetic parameters from in vitro experimental data. This study also demonstrated that in vitro experimental data in humans and rats were important information for predicting human in vivo hepatic clearance, and the additional rat in vivo data were not significant for prediction with the information of molecular descriptors. These results imply that the present method can be useful for highthroughput drug candidate screening by reducing the time and cost in the early stage of the drug discovery process.