title: Evaluation of the artificial membrane permeability of drugs by digital simulation.
abstract: A digital simulation method has been developed for evaluating the membrane permeability of drugs in the parallel artificial membrane permeation assay (PAMPA). The simulation results have shown that the permeability coefficient (log Ppampa) of drugs is linearly increased with increasing their distribution coefficient (log KD,M) to the lipid membrane, i.e., the hydrophobicity of the drug molecules. However, log Ppampa shows signs of leveling off for highly hydrophobic drugs. Such a dependence of log Ppampa is in harmony with the reported experimental data, and has been well explained in terms of the change in the rate-determining step from the diffusion in the membrane to that in the unstirred water layer (UWL) on both sides of the membrane. Additionally, the effects of several factors, including lag time, diffusion coefficient, pH, and pKa, on the permeability coefficient have been well simulated. It has thus been suggested that the proposed method should be promising for in silico evaluation of the membrane permeability of drugs.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe 657-8501, Japan. Electronic address: nakamuramayumi923@gmail.com.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe 657-8501, Japan. Electronic address: osakai@kobe-u.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Osakai
mesh_terms: D003198:Computer Simulation; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008567:Membranes, Artificial; D008962:Models, Theoretical; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations
keywords: Digital simulation; PAMPA; Permeability coefficient