Skin Pigmentation’s Impact on Drug Efficacy and Safety

In the world of medicine, the efficacy and safety of drugs are often viewed as universal. However, recent research challenges this notion by revealing how skin pigmentation might influence drug interactions. The surprising findings suggest that skin pigmentation acts much like a “sponge,” absorbing certain drug compounds and altering their bioavailability and effectiveness. This insight, shared by Simon Groen and Sophie Zaaijer from the University of California, Riverside, opens the door to a more nuanced understanding of drug administration and its effects across diverse populations.

Melanin, the pigment responsible for skin color, shows a surprising affinity for certain drug compounds, according to Groen, an assistant professor at UC Riverside. His findings, published in the journal Human Genomics, highlight the overlooked role of melanin in drug safety and dosing, raising vital questions about the standard dose prescribed across all skin tones. “Our review paper concludes that melanin, the pigment responsible for skin color, shows a surprising affinity for certain drug compounds,” says Groen. This lack of consideration can lead to differences in drug efficacy among people with varying skin tones, potentially affecting up to 20% of medications.

The current guidelines by the FDA on toxicity testing fall short in addressing the impact of skin pigmentation on drug interactions, notes Zaaijer, a consultant specializing in diversity, equity, and inclusion in preclinical R&D. Despite the FDA’s emphasis on diversity in clinical trials, their early-stage practices mainly focus on populations of Northern European descent, which may not represent the diversity found in the broader population. This creates a pressing need for an inclusive approach to drug development.

One noteworthy example involves nicotine, where its affinity for skin pigments might impact smoking habits among different skin tones, posing significant questions about the efficiency of nicotine patches for individuals with darker skin tones. This potential discrepancy has prompted Groen and Zaaijer to call for the consideration of skin pigmentation in safety and dosing estimates, advocating for the use of human 3D skin models with varied pigmentation levels to accurately assess drug binding properties across skin types.

The research underscores a transformative moment in the biomedical industry, where inclusivity is no longer optional but a requisite. As part of this shift, the researchers acknowledge the importance of aligning FDA guidelines with their Diversity Action Plan to ensure equitable drug development. This alignment will necessitate collaboration across academia, industry researchers, clinicians, and regulators to overcome silos and enhance trust in drug development processes.

The urgency is underscored by the recent enactment of the Food and Drug Omnibus Reform Act in 2022, with the FDA’s draft guidelines soon mandating the consideration of patient diversity in clinical trials and preclinical R&D. As these guidelines become finalized, the focus will move towards specifying which pharmacokinetic variables should be tested in the drug R&D pipeline to ensure equity across diverse populations.

Groen and Zaaijer urge the pharmaceutical industry, academia, patient advocacy groups, and clinical participants to be proactive in questioning the suitability of drugs across different ancestries. They foresee this as a critical step towards achieving an inclusive and trustworthy drug development process.

In conclusion, the implications of skin pigmentation on drug efficacy and safety present a compelling challenge for the future of medicine. With the right adaptations, the industry stands to foster greater inclusivity, equity, and trust, paving the way for more effective and fair treatment options for all. As Groen aptly puts it, considering different ancestral backgrounds in the early stages of drug discovery will build trust and encourage diverse participation in clinical trials, crucial for the progress of equitable medicine.