Can models of percutaneous absorption based on in vitro data in frogs predict in vivo absorption?

Llewelyn, Victoria K., Berger, Lee, and Glass, Beverley D. (2020) Can models of percutaneous absorption based on in vitro data in frogs predict in vivo absorption? PLoS ONE, 15 (7). e0235737.

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The primary aim of in vitro testing of chemicals delivered via the percutaneous route is to predict the absorption that would ensue if exposure occurred in live animals. While there is mounting evidence that in vitro diffusion studies in mammalian skin can provide valid information regarding likely in vivo absorption, little is known whether such a correlation exists between in vitro diffusion testing and in vivo blood levels in amphibians. The current study used previously-reported in vitro absorption data for caffeine, benzoic acid, and ibuprofen across isolated skin from the cane toad (Rhinella marina) to produce a series of linear mixed-effect models of the absorption parameters flux and permeability coefficient (K-p). Models investigated the relative impacts of animal weight, physicochemical characteristics of the applied chemical (logP or molecular weight), and site of application. The top models were then used to predict the flux, K(p)and serum concentrations of the same three model chemicals. Finally, the absorption of these chemicals was determined in live cane toads, and results compared to the model predictions. LogP and site of application were included in all top models. In vivo absorption rates were lower than predicted for all chemicals, however, the models provided reasonable predictions of serum concentration, with factors of difference (FOD) ranging from 2.5-10.5. Ibuprofen, the chemical with the highest relative lipophilicity, had the poorest predictive performance, consistently having the highest FOD for all predictions. This report presents the first models of percutaneous absorption in an amphibian. These models provide a basic method to establish the approximate in vivo absorption of hydrophilic and moderately-lipophilic chemicals through frog skin, and could therefore be used to predict absorption when formulating such chemicals for treatment of disease in frogs, or for risk-assessments regarding chemical pollutants in frog habitats.

Item ID: 64168
Item Type: Article (Research - C1)
ISSN: 1932-6203
Copyright Information: © 2020 Llewelyn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Date Deposited: 26 Aug 2020 07:32
FoR Codes: 31 BIOLOGICAL SCIENCES > 3109 Zoology > 310907 Animal physiological ecology @ 100%
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