A Mechanistic Bayesian Inferential Workflow for Estimation of In Vivo Skin Permeation from In Vitro Measurements
Journal of Pharmaceutical Sciences, ISSN: 0022-3549, Vol: 111, Issue: 3, Page: 838-851
2022
- 7Citations
- 4Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations7
- Citation Indexes7
- Captures4
- Readers4
Article Description
Computational models can play an integral role in the chemical risk assessment of dermatological products. However, a limitation on the ability of mathematical models to extrapolate from in vitro measurements to in human predictions arises from context-dependence: modeling assumptions made in one setting may not carry over to another scenario. Mechanistic models of dermal absorption relate the skin penetration kinetics of permeants to their partitioning and diffusion across elementary sub-compartments of the skin. This endows them with a flexibility through which specific model components can be adjusted to better reflect dermal absorption in contexts that differ from the in vitro setting, while keeping fixed any context-invariant parameters that remain unchanged in the two scenarios. This paper presents a workflow for predicting in vivo dermal absorption by integrating a mechanistic model of skin penetration with in vitro permeation test (IVPT) measurements. A Bayesian approach is adopted to infer a joint posterior distribution of context-invariant model parameters. By populating the model with samples of context-invariant parameters from this distribution and adjusting context-dependent parameters to suit the in vivo setting, simulations of the model yield estimates of the likely range of in vivo dermal absorption given the IVPT data. This workflow is applied to five compounds previously tested in vivo. In each case, the range of in vivo predictions encompassed the range observed experimentally. These studies demonstrate that the proposed workflow enables the derivation of mechanistically derived upper bounds on dermal absorption for the purposes of chemical risk assessment.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0022354921006511; http://dx.doi.org/10.1016/j.xphs.2021.11.028; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85121845602&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/34871561; https://linkinghub.elsevier.com/retrieve/pii/S0022354921006511; https://dx.doi.org/10.1016/j.xphs.2021.11.028
Elsevier BV
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