Dynamics of diffusion with reversible binding in microscopically heterogeneous membranes: General theory and applications to dermal penetration

“…In the latter, approximately 80% of the volume is accessible water around the keratin filaments. By a recent correlation of partitioning data,7 these factors yield the estimate for the tissue‐average partition coefficient of free (unbound) TH relative to an aqueous solution maintaining the unionized form9 (see Appendix A, Eqs. A5–A7 of this reference).…”

Section: Methodsmentioning

confidence: 99%

Tissue Binding Affects the Kinetics of Theophylline Diffusion Through the Stratum Corneum Barrier Layer of Skin

Frasch

Barbero

Hettick

et al. 2011

Journal of Pharmaceutical Sciences

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“…Drug binds to keratin in the skin [7] and the dynamics of binding in the skin have been shown to be linear [14] . As only unbound drug is free to diffuse [5] , binding may be an important factor in the formation of a SC reservoir. We therefore consider both bound and unbound drug in the SC and allow for the possibility of binding and unbinding.…”

Section: Modelmentioning

confidence: 99%

“…As only unbound drug diffuses [5] the cause of a reservoir forming in the SC is thought to be high keratin binding and slow desorption kinetics [5] . Binding within the skin is most typical for lipophilic drugs with high molecular weight [6,7] .…”

Section: Introductionmentioning

confidence: 99%

A mechanistic approach to modelling the formation of a drug reservoir in the skin

Jones

White

Delgado‐Charro

2016

Mathematical Biosciences

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It has been shown that prolonged systemic presence of a drug can cause a build-up of that drug in the skin. This drug 'reservoir', if properly understood, could provide useful information about recent drug-taking history of the patient. We create a pair of coupled mathematical models which combine to explore the potential for a drug reservoir to establish based on the kinetic properties of the drug. The first compartmental model is used to characterise time-dependent drug concentrations in plasma and tissue following a customisable drug regimen. Outputs from this model provide boundary conditions for the second, spatio-temporal model of drug build-up in the skin. We focus on drugs that are highly bound as this will restrict their potential to move freely into the skin but which are lipophilic so that, in the unbound form, they would demonstrate an affinity to the outer layers of the skin. Buprenorphine, a drug used to treat opiate addiction, is one example of a drug satisfying these properties. In the discussion we highlight how our study might be used to inform future experimental design and data collection to provide relevant parameter estimates for reservoir formation and its potential to contribute to enhanced drug monitoring techniques.

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Dynamics of diffusion with reversible binding in microscopically heterogeneous membranes: General theory and applications to dermal penetration

Cited by 26 publications

References 71 publications

Finite dose skin mass balance including the lateral part: Comparison between experiment, pharmacokinetic modeling and diffusion models

Finite dose skin mass balance including the lateral part: Comparison between experiment, pharmacokinetic modeling and diffusion models

Tissue Binding Affects the Kinetics of Theophylline Diffusion Through the Stratum Corneum Barrier Layer of Skin

A mechanistic approach to modelling the formation of a drug reservoir in the skin

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