Implementing differentially pigmented skin models for predicting drug response variability across human ancestries.

Area of Science:

• Pharmacology and Toxicology
• Dermatology
• Health Equity

Background:

• Racial disparities in health outcomes are a growing concern, prompting legislative and scientific attention.
• The role of melanin-based skin pigmentation in drug binding and its subsequent effects on therapeutic efficacy and adverse drug reactions are not well understood.
• Existing research often fails to account for variations in skin pigmentation, potentially leading to inequitable pharmacological outcomes.

Purpose of the Study:

• To examine the complex interactions between melanin-based skin pigmentation and drug pharmacokinetics and pharmacodynamics.
• To emphasize the importance of considering skin pigmentation diversity in pharmacological research.
• To advocate for the advancement of equitable pharmacological interventions.

Main Methods:

• Literature review and synthesis of existing research on skin pigmentation, pharmacokinetics, and pharmacodynamics.
• Analysis of the impact of melanin's drug-binding properties on therapeutic outcomes.
• Development of guidelines for selecting New Approach Methods (NAMs) for preclinical studies.

Main Results:

• Melanin's properties influence how drugs are absorbed, distributed, metabolized, and excreted.
• Lack of consideration for skin pigmentation diversity can lead to suboptimal drug efficacy and increased adverse events in certain populations.
• New Approach Methods (NAMs) can be utilized to create more inclusive preclinical study designs.

Conclusions:

• Incorporating skin pigmentation as a variable is essential for achieving equity in pharmacology.
• Inclusive preclinical study designs using NAMs can improve the translatability of drug findings to diverse clinical populations.
• Addressing these gaps will enhance the safety and effectiveness of pharmacological treatments across all individuals.