The present study demonstrated that the information of molecular descriptors of drugs increases the accuracy of predicting humanin vivo hepatic clearance fromin 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 usingin 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 humanin vivo pharmacokinetic parameters fromin vitro experimental data. This study also demonstrated thatin vitro experimental data in humans and rats were important information for predicting humanin vivo hepatic clearance, and the additional ratin vivo data were not significant for prediction with the information of molecular descriptors. These results imply that the present method can be useful for high-throughput drug candidate screening by reducing the time and cost in the early stage of the drug discovery process.
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Lee, S., Kim, D. Equation chapter 1 section 1A new method for predicting human hepatic clearance fromin Vitro experimental data using molecular descriptors. Arch Pharm Res 30, 182–190 (2007). https://doi.org/10.1007/BF02977693
- Hepatic clearance
- In vitro data
- Molecular descriptors
- Multiple linear regression