Next Article in Journal
O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions
Previous Article in Journal
Reference Gene Selection in the Desert Plant Eremosparton songoricum
 
 
Article

A Novel Chemometric Method for the Prediction of Human Oral Bioavailability

by 1,2,†, 1,†, 2, 3, 2, 2,*, 1,* and 4
1
College of Science, Northwest A & F University, Yangling 712100, China
2
College of Life Science, Northwest A & F University, Yangling 712100, China
3
School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China
4
Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2012, 13(6), 6964-6982; https://doi.org/10.3390/ijms13066964
Received: 15 May 2012 / Revised: 29 May 2012 / Accepted: 29 May 2012 / Published: 7 June 2012
Orally administered drugs must overcome several barriers before reaching their target site. Such barriers depend largely upon specific membrane transport systems and intracellular drug-metabolizing enzymes. For the first time, the P-glycoprotein (P-gp) and cytochrome P450s, the main line of defense by limiting the oral bioavailability (OB) of drugs, were brought into construction of QSAR modeling for human OB based on 805 structurally diverse drug and drug-like molecules. The linear (multiple linear regression: MLR, and partial least squares regression: PLS) and nonlinear (support-vector machine regression: SVR) methods are used to construct the models with their predictivity verified with five-fold cross-validation and independent external tests. The performance of SVR is slightly better than that of MLR and PLS, as indicated by its determination coefficient (R2) of 0.80 and standard error of estimate (SEE) of 0.31 for test sets. For the MLR and PLS, they are relatively weak, showing prediction abilities of 0.60 and 0.64 for the training set with SEE of 0.40 and 0.31, respectively. Our study indicates that the MLR, PLS and SVR-based in silico models have good potential in facilitating the prediction of oral bioavailability and can be applied in future drug design. View Full-Text
Keywords: oral bioavailability; quantitative structure activity relationship; cytochrome P4503A4 and P4502D6; P-glycoprotein oral bioavailability; quantitative structure activity relationship; cytochrome P4503A4 and P4502D6; P-glycoprotein
Show Figures

MDPI and ACS Style

Xu, X.; Zhang, W.; Huang, C.; Li, Y.; Yu, H.; Wang, Y.; Duan, J.; Ling, Y. A Novel Chemometric Method for the Prediction of Human Oral Bioavailability. Int. J. Mol. Sci. 2012, 13, 6964-6982. https://doi.org/10.3390/ijms13066964

AMA Style

Xu X, Zhang W, Huang C, Li Y, Yu H, Wang Y, Duan J, Ling Y. A Novel Chemometric Method for the Prediction of Human Oral Bioavailability. International Journal of Molecular Sciences. 2012; 13(6):6964-6982. https://doi.org/10.3390/ijms13066964

Chicago/Turabian Style

Xu, Xue, Wuxia Zhang, Chao Huang, Yan Li, Hua Yu, Yonghua Wang, Jinyou Duan, and Yang Ling. 2012. "A Novel Chemometric Method for the Prediction of Human Oral Bioavailability" International Journal of Molecular Sciences 13, no. 6: 6964-6982. https://doi.org/10.3390/ijms13066964

Find Other Styles

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Back to TopTop