title: Development of novel in silico model to predict corneal permeability for congeneric drugs: a QSPR approach.
abstract: This study was undertaken to determine in vivo permeability coefficients for fluoroquinolones and to assess its correlation with the permeability derived using reported models in the literature. Further, the aim was to develop novel QSPR model to predict corneal permeability for fluoroquinolones and test its suitability on other training sets. The in vivo permeability coefficient was determined using cassette dosing (N-in-One) approach for nine fluoroquinolones (norfloxacin, ciprofloxacin, lomefloxacin, ofloxacin, levofloxacin, sparfloxacin, pefloxacin, gatifloxacin, and moxifloxacin) in rabbits. The correlation between corneal permeability derived using in vivo studies with that derived from reported models was determined. Novel QSPR-based model was developed using in vivo corneal permeability along with other molecular descriptors. The suitability of developed model was tested on β-blockers (n = 15). The model showed better prediction of corneal permeability for fluoroquinolones (r(2) > 0.9) as well as β-blockers (r(2) > 0.6). The newly developed QSPR model based upon in vivo generated data was found suitable to predict corneal permeability for fluoroquinolones as well as other sets of compounds.
authors.affiliation: Department of Ocular Pharmacology and Pharmacy, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Charu
authors.initials: C
authors.lastname: Sharma
authors.forename: Thirumurthy
authors.initials: T
authors.lastname: Velpandian
authors.forename: Nihar Ranjan
authors.initials: NR
authors.lastname: Biswas
authors.forename: Niranjan
authors.initials: N
authors.lastname: Nayak
authors.forename: Rasik Bihari
authors.initials: RB
authors.lastname: Vajpayee
authors.forename: Supriyo
authors.initials: S
authors.lastname: Ghose
mesh_terms: D000465:Algorithms; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D003315:Cornea / Q000378:metabolism*; D016568:Drugs, Generic / Q000737:chemistry / Q000493:pharmacokinetics*; D024841:Fluoroquinolones / Q000737:chemistry / Q000493:pharmacokinetics*; D008954:Models, Biological; D010539:Permeability; D021281:Quantitative Structure-Activity Relationship; D011817:Rabbits
chemical_list: D000900:Anti-Bacterial Agents; D016568:Drugs, Generic; D024841:Fluoroquinolones