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Physiologically relevant two-compartment pharmacokinetic models for skin.

K D McCarley1, A L Bunge

  • 1Chemical Engineering and Petroleum Refining Department, Colorado School of Mines, Golden, Colorado 80401, USA.

Journal of Pharmaceutical Sciences
|August 16, 2000
PubMed
Summary

This study introduces two-compartment pharmacokinetic models for skin, improving predictions of chemical absorption. Model B2, using characteristic times, better represents skin layers (stratum corneum and viable epidermis) than Model B1.

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Area of Science:

  • Dermal pharmacokinetics
  • Mathematical modeling of skin absorption

Background:

  • Pharmacokinetic models are crucial for predicting chemical absorption through the skin.
  • For lipophilic chemicals, both the stratum corneum (SC) and viable epidermis (VE) significantly impede penetration, necessitating their inclusion in models.

Purpose of the Study:

  • To develop and compare two-compartment pharmacokinetic models for skin, separately representing the SC and VE.
  • To extend existing one-compartment model procedures for enhanced accuracy in dermal absorption prediction.

Main Methods:

  • Developed two-compartment models by extending procedures for one-compartment models.
  • Matched characteristics of two-compartment models with a two-membrane model of the skin.
  • Compared compartment models against membrane representations for various dermal exposure scenarios.

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Main Results:

  • The two-compartment model using characteristic times (Model B2) closely represents the two-membrane model when valid for chemical exposure scenarios.
  • The model developed using equilibrium conditions (Model B1) is recommended when Model B2 is invalid.
  • Provided criteria for selecting between one- and two-compartment model options.

Conclusions:

  • Two-compartment pharmacokinetic models offer improved representation of skin layers for chemical absorption analysis.
  • Model B2 is generally preferred for its accuracy, while Model B1 serves as a viable alternative under specific conditions.
  • The study provides guidance for selecting appropriate skin pharmacokinetic models based on exposure scenarios.