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: Megan E Sawyer, Marina V Evans, Charles A Wilson, Lauren J Beesley, Lider S Leon, Chris R Eklund, Edward L Croom, Rex A Pegram
• Journal: Toxicology letters (Toxicol Lett) Vol. 245 Pg. 106-9 (Mar 14 2016) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 26794662 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Insecticides
• Hexachlorocyclohexane

Topics

• Algorithms
• Diffusion
• Hexachlorocyclohexane (pharmacokinetics)
• Humans
• Insecticides (pharmacokinetics)
• Lipid Metabolism
• Models, Biological
• Permeability
• Protein Binding
• Skin (metabolism)
• Skin Absorption