Andrews, C.W., Bennett, L. & Yu, L.X. Pharm Res (2000) 17: 639. doi:10.1023/A:1007556711109
Purpose. The purpose of this investigation was to develop aquantitative structure-bioavailability relationship (QSBR) model for drugdiscovery and development.
Methods. A database of drugs with human oral bioavailability wasassembled in electronic form with structure in SMILES format. Usingthat database, a stepwise regression procedure was used to link oralbioavailability in humans and substructural fragments in drugs. Theregression model was compared with Lipinski's Rule of Five.
Results. The human oral bioavailability database contains 591compounds. A regression model employing 85 descriptors was built topredict the human oral bioavailability of a compound based on itsmolecular structure. Compared to Lipinski's Rule of Five, the falsenegative predictions were reduced from 5;pc to 3;pc while the falsepositive predictions decreased from 78;pc to 53;pc. A set of substructuraldescriptors was identified to show which fragments tend toincrease/decrease human oral bioavailability.
Conclusions. A novel quantitative structure-bioavailabilityrelationship (QSBR) was developed. Despite a large degree of experimentalerror, the model was reasonably predictive and stood up tocross-validation. When compared to Lipinski's Rule of Five, the QSBRmodel was able to reduce false positive predictions.
bloavailability quantitative structure-bioavailability relationship Lipinaki's rule of Five