title: Prediction of bioavailability of selected bisphosphonates using in silico methods towards categorization into a biopharmaceutical classification system.
abstract: The physicochemical properties relevant to biological activity of selected bisphosphonates such as clodronate disodium salt, etidronate disodium salt, pamidronate disodium salt, alendronate sodium salt, ibandronate sodium salt, risedronate sodium salt and zoledronate disodium salt were determined using in silico methods. The main aim of our research was to investigate and propose molecular determinants thataffect bioavailability of above mentioned compounds. These determinants are: stabilization energy (deltaE), free energy of solvation (deltaG(solv)), electrostatic potential, dipole moment, as well as partition and distribution coefficients estimated by the log P and log D values. Presented values indicate that selected bisphosphonates a recharacterized by high solubility and low permeability. The calculated parameters describing both solubility and permeability through biological membranes seem to be a good bioavailability indicators of bisphosphonates examined and can be a useful tool to include into Biopharmaceutical Classification System (BCS) development.
authors.affiliation: Medical University of Warsaw, Department of Drug Chemistry, 1 Banacha St., Warszawa 02-097, Poland. joanna@biernaccy.net
authors.forename: Joanna
authors.initials: J
authors.lastname: Biernacka
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Betlejewska-Kielak
authors.forename: Ewa
authors.initials: E
authors.lastname: Kłosińska-Szmurło
authors.forename: Franciszek A
authors.initials: FA
authors.lastname: Pluciński
authors.forename: Aleksander P
authors.initials: AP
authors.lastname: Mazurek
mesh_terms: D001682:Biological Availability; D001702:Biopharmaceutics / Q000145:classification* / Q000379:methods*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000145:classification / Q000493:pharmacokinetics*; D003198:Computer Simulation; D004164:Diphosphonates / Q000008:administration & dosage / Q000145:classification / Q000493:pharmacokinetics*; D008958:Models, Molecular; D010539:Permeability; D012995:Solubility; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates