title: Drug permeability prediction using PMF method.
abstract: Drug permeability determines the oral availability of drugs via cellular membranes. Poor permeability makes a drug unsuitable for further development. The permeability may be estimated as the free energy change that the drug should overcome through crossing membrane. In this paper the drug permeability was simulated using molecular dynamics method and the potential energy profile was calculated with potential of mean force (PMF) method. The membrane was simulated using DPPC bilayer and three drugs with different permeability were tested. PMF studies on these three drugs show that doxorubicin (low permeability) should pass higher free energy barrier from water to DPPC bilayer center while ibuprofen (high permeability) has a lower energy barrier. Our calculation indicates that the simulation model we built is suitable to predict drug permeability.
authors.affiliation: State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, People's Republic of China. fancuimeng@yahoo.com.cn
authors.forename: Fancui
authors.initials: F
authors.lastname: Meng
authors.forename: Weiren
authors.initials: W
authors.lastname: Xu
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000378:metabolism; D000959:Antihypertensive Agents / Q000378:metabolism; D001262:Atenolol / Q000378:metabolism; D018938:Caco-2 Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology*; D004317:Doxorubicin / Q000378:metabolism; D006801:Humans; D007052:Ibuprofen / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000903:Antibiotics, Antineoplastic; D000959:Antihypertensive Agents; D004364:Pharmaceutical Preparations; D001262:Atenolol; D004317:Doxorubicin; D007052:Ibuprofen