Pharmacokinetic models of dermal absorption

Area of Science:

• Pharmacokinetics
• Dermal Absorption
• Computational Modeling

Background:

• Pharmacokinetic (compartment) models are widely used for skin absorption analysis.
• Previous models lacked clear definitions of rate constants, stated assumptions, and specified skin layers, hindering comparisons.
• Physicochemical and physical properties of the skin are crucial for accurate dermal absorption predictions.

Purpose of the Study:

• To review and compare published one- and two-compartment skin models.
• To present models with consistent nomenclature, clearly defined assumptions, and expressed rate constants.
• To compare compartment models against a more functionally representative two-membrane skin model.

Main Methods:

• Review and comparison of nine one-compartment and two two-compartment models.
• Expression of rate constants using physicochemical properties (diffusion, partition coefficients, thickness).
• Estimation methods for required physicochemical parameters were summarized.
• Comparison with calculations from a two-membrane skin model.

Main Results:

• Eleven compartment models were analyzed and compared.
• Many compartment models failed to predict key characteristics of the two-membrane model, including blood flow effects.
• Kubota's and McCarley's models demonstrated better prediction accuracy for the two-membrane model.

Conclusions:

• Standardized comparison of skin pharmacokinetic models is essential.
• The two-membrane model offers a more accurate representation of skin function and dermal absorption.
• Specific compartment models (Kubota, McCarley) show improved predictive capabilities by aligning with membrane model characteristics.