Modelling dermal drug distribution after topical application in human.

Area of Science:

• Pharmacokinetics
• Dermal Drug Delivery
• Physiological Modeling

Background:

• Topical drug application is key for treating local skin conditions.
• Understanding drug distribution in the dermis and underlying tissues is essential for optimizing efficacy.
• Current models may not fully account for all transport mechanisms.

Purpose of the Study:

• To develop a physiological pharmacokinetic model for topical drug distribution.
• To interpret in vivo human data on dermal drug penetration.
• To elucidate the roles of blood flow, protein binding, and dermal binding in drug transport.

Main Methods:

• Created a novel physiological pharmacokinetic model.
• Incorporated parameters like blood flow, protein binding, and dermal binding.
• Validated the model using in vivo human biopsy data and in vitro dermal penetration studies.

Main Results:

• Dermal diffusion alone is insufficient to explain observed in vivo drug concentrations.
• Blood and/or lymphatic transport significantly contribute to deep tissue drug distribution.
• This was observed for the majority of the tested topical substances.

Conclusions:

• Topical drug delivery strategies must consider blood and lymphatic transport.
• For certain compounds, these transport mechanisms may be more critical than dermal diffusion.
• Optimized topical drug delivery systems should account for systemic transport pathways.