A simple model for the prediction of corneal permeability

Prediction of the Corneal Permeability of Drug-Like Compounds

“…In contrast to some previous studies (12,32), we did not find that molecular weight or volume was an important parameter for the corneal permeability, even though molecular weight is known to affect the permeation across pure lipid bilayers (34). This is explained first by the relatively low variance in molecular weight of the compounds in the data set (167-361 g/mol).…”

“…The only compound that we excluded from this study was acebutolol, whose corneal permeability has been reported by two sources included in this study (4,18). Previously, it has been identified as an outlier in modeling studies (12,13), and, recently, acebutolol has been reported to be actively transported by MDR-1 in rabbit cornea (38).…”

“…Even though quantitative structure-property relationship (QSPR) models for transdermal and intestinal absorption of drugs have been constructed (8)(9)(10), QSPR models for the corneal permeability are still at an elementary level. Some computational models for predicting the corneal permeability have been developed (2,(11)(12)(13)(14), but so many of these models have been constructed for a small set of similar compounds (2,13), and the models are thus not applicable to a broader variety of molecules. Other models use descriptors that are difficult to obtain, like delta logP, the difference between the octanol-water partition coefficient and the alkane-water partition coefficient (11).…”

MI-QSAR models for prediction of corneal permeability of organic compounds1

“…Calculation of descriptors Most of the intramolecular solute descriptors were calculated by using the commercial software package CS Chem3D Ultra 7.0 (Chemoffice 2002; Cambridgesoft, Cambridge, MA, USA), which included molecular mechanism (MM) parameters (such as bending energy, torsion energy and van der Waals energy), quantum chemistry parameters (such as electronic energy, HOMO, and LUMO energy), hydrophobic parameters (such as Clog P), and stereo parameters (such as Es and Balaban index). The data of Q O,N and Q H comes from Fu and Liang's study [20] . The intermolecular solute-membrane interaction descriptors were extracted directly from the MDS trajectories in which the solute-membrane complex had the lowest energy geometry.…”

“…However, ∆log P values are usually difficult to obtain. Therefore, Fu and Liang attempted to predict the corneal permeabilities of miscellaneous compounds from simpler parameters [20] . They primarily considered charge parameters and solid parameters and constructed a better model (R= 0.921, S=0.233), which included β-blockers, steroids and other structurally different compounds.…”