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Related Concept Videos

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In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
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Physiological pharmacokinetic models, often called flow-limited or perfusion models, typically assume a swift drug distribution between tissue and venous blood, creating a rapid drug equilibrium. This premise is based on the idea that drug diffusion is extremely fast, and the cell membrane presents no barrier to drug permeation. In this scenario, where no drug binding occurs, the drug concentration in the tissue equals that of the venous blood leaving the tissue. This greatly simplifies the...
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Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging
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Comparative Study of Dermal Pharmacokinetics Between Topical Drugs Using Open Flow Microperfusion in a Pig Model.

Manfred Bodenlenz1, Thean Yeoh2, Gabriel Berstein2

  • 1HEALTH - Institute for Biomedical Research and Technologies, Joanneum Research Forschungsgesellschaft M.B.H, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.

Pharmaceutical Research
|December 29, 2023
PubMed
Summary

Dermal open flow microperfusion (dOFM) in pigs accurately measures unbound drug in interstitial fluid, offering a more reliable dermal exposure assessment than biopsies for topical drug development.

Keywords:
candidatesclinical efficacycompoundsfree drug hypothesisin vivo animal model

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Area of Science:

  • Pharmacology
  • Dermatology
  • Drug Development

Background:

  • Accurate dermal pharmacokinetics are crucial for successful topical drug development.
  • Assessing drug exposure in the skin is challenging with traditional methods.

Purpose of the Study:

  • To evaluate dermal open flow microperfusion (dOFM) as a reliable method for measuring dermal drug exposure in vivo.
  • To compare dOFM-derived unbound drug concentrations with dermal biopsy measurements.
  • To validate dOFM methodology and assess the impact of dosing parameters.

Main Methods:

  • A pig model was used to administer seven different drugs topically.
  • Dermal interstitial fluid concentrations were measured using dOFM (total and unbound).
  • Dermal biopsies were analyzed for total drug concentrations.

Main Results:

  • dOFM demonstrated high precision and reproducibility in distinguishing drug concentrations.
  • Biopsy measurements yielded higher and more variable drug concentrations.
  • dOFM results were consistent with a recirculation approach.

Conclusions:

  • The dOFM pig model provides a robust and reproducible method for direct measurement of topical drug concentrations in dermal interstitial fluid.
  • dOFM is a more reliable indicator of dermal exposure compared to biopsies.
  • Biopsies may overestimate exposure due to bound drug and appendage association.