title: Development of a human physiologically based pharmacokinetic (PBPK) model for dermal permeability for lindane.
abstract: Lindane is a neurotoxicant used for the treatment of lice and scabies present on human skin. Due to its pharmaceutical application, an extensive pharmacokinetic database exists in humans. Mathematical diffusion models allow for calculation of lindane skin permeability coefficients using human kinetic data obtained from in vitro and in vivo experimentation as well as a default compound-specific calculation based on physicochemical characteristics used in the absence of kinetic data. A dermal model was developed to describe lindane diffusion into the skin, where the skin compartment consisted of homogeneous dermal tissue. This study utilized Fick's law of diffusion along with chemical binding to protein and lipids to determine appropriate dermal absorption parameters which were then incorporated into a physiologically based pharmacokinetic (PBPK) model to describe in vivo kinetics. The estimation of permeability coefficients using chemical binding in combination with in vivo data demonstrates the advantages of combining physiochemical properties with a PBPK model to predict dermal absorption.
authors.affiliation: Department of Mathematics, Campus Box 8205, North Carolina State University, Raleigh, NC 27695, USA. Electronic address: m.sawyer@snhu.edu.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Sawyer
authors.affiliation: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Office of Research and Development, Research Triangle Park, NC 27709, USA.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Evans
authors.affiliation: Research Experience for Undergraduate participant, Department of Mathematics, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Wilson
authors.affiliation: Research Experience for Undergraduate participant, Department of Mathematics, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Beesley
authors.affiliation: Research Experience for Undergraduate participant, Department of Mathematics, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Lider S
authors.initials: LS
authors.lastname: Leon
authors.affiliation: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Office of Research and Development, Research Triangle Park, NC 27709, USA.
authors.forename: Chris R
authors.initials: CR
authors.lastname: Eklund
authors.affiliation: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Office of Research and Development, Research Triangle Park, NC 27709, USA.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Croom
authors.affiliation: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Office of Research and Development, Research Triangle Park, NC 27709, USA.
authors.forename: Rex A
authors.initials: RA
authors.lastname: Pegram
mesh_terms: D000465:Algorithms; D004058:Diffusion; D001556:Hexachlorocyclohexane / Q000493:pharmacokinetics*; D006801:Humans; D007306:Insecticides / Q000493:pharmacokinetics*; D050356:Lipid Metabolism; D008954:Models, Biological; D010539:Permeability; D011485:Protein Binding; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption
chemical_list: D007306:Insecticides; D001556:Hexachlorocyclohexane
keywords: Dermal permeability; Lindane; PBPK