Your skin tone could affect how well your medication works!

Skin is composed of multiple layers, from the innermost stratum basale that contains the melanocytes to intermediate layers dominated by keratinocytes and the outermost stratum corneum. The melanocytes produce the melanin-containing melanosomes, which show an approximately 10 times difference in accumulation between individuals with dark and light skin tones. The melanosomes are transferred to the keratinocytes, where they surround the nucleus and protect DNA from UV-induced damage. B This simplified model posits that differential drug responses between human genetic ancestry groups [1] could result from influences of a combination of both the genotype for drug metabolic enzymes and skin eumelanin level of an individual (visible as skin tone) on the bioavailability of drugs.

Credit: Human Genomics (2024). DOI: 10.1186/s40246-024-00677-7

Skin pigmentation may act as a "sponge" for some medications, potentially influencing the speed with which active drugs reach their intended targets, a pair of scientists report in a perspective article published in the journal Human Genomics.

The researchers argue that a sizable proportion of drugs and other compounds can bind to melanin pigments in the skin, leading to differences in how bioavailable and efficacious these drugs and other compounds are in people with varying skin tones.

The  review paper concludes that melanin, the pigment responsible for skin color, shows a surprising affinity for certain drug compounds. Melanin's implications for drug safety and dosing have been largely overlooked, raising alarming questions about the efficacy of standard dosing since people vary a lot in skin tones.

Current  guidelines for toxicity testing fail to adequately address the impact of skin pigmentation on drug interactions.

This oversight is particularly concerning given the push for more diverse clinical trials, as outlined in the agency's Diversity Action Plan. But current early-stage drug development practices still primarily focus on drug testing in white populations of Northern European descent.

In one example, the researchers found evidence of nicotine affinity for skin pigments, potentially affecting smoking habits among people with a variety of skin tones and raising questions about the efficacy of skin-adhered nicotine patches for smoking cessation.

"Are we inadvertently shortchanging smokers with darker skin tones if they turn to these patches in their attempts to quit?" , the researchers ask. They propose utilizing a new workflow involving human 3D skin models with varying pigmentation levels that could offer pharmaceutical companies an efficient method to assess drug binding properties across different skin types.

Skin pigmentation should be considered as a factor in safety and dosing estimates. "We stand on the brink of a transformative era in the biomedical industry, where embracing inclusivity is not just an option anymore but a necessity," they argue.

According to the researchers, skin pigmentation is just one example. Genetic variations among minority groups can lead to starkly different drug responses across races and ethnicities, affecting up to 20% of all medications, they said.

Yet, our molecular understanding of these differences remains very limited.

The researchers acknowledge that transformations enhancing inclusivity—encompassing race, ethnicity, sex, and age—demand a comprehensive overhaul of all  guidelines on clinical endpoints to align with the  Diversity Action Plan.

The researchers hope to activate the pharmaceutical industry and academia to start doing systematic experimental evaluations in preclinical research in relation to skin pigmentation and drug kinetics.

They also encourage patients, their advocacy groups, and clinical trial participants to ask questions related to ancestry-specific drug efficacy and safety, such as "Has this drug been tested to see if it's safe for people from different ancestral backgrounds, including mine?" Clinicians and pharmaceutical representatives should be able to provide an easy-to-understand document outlining the results of the various tests, the researchers said.

They acknowledge, though,  that in the current state of drug development this will be hard.

Sophie Zaaijer et al, Implementing differentially pigmented skin models for predicting drug response variability across human ancestries, Human Genomics (2024). DOI: 10.1186/s40246-024-00677-7