Skin pigmentation might serve as a “sponge” for certain medications, which could impact how quickly active drugs reach their targets, according to findings by two scientists.
Skin pigmentation might act like a “sponge” for some medications, possibly affecting how quickly active drugs target their intended areas, as noted in a perspective article in the journal Human Genomics by a pair of scientists.
The researchers suggest that a significant number of drugs and other substances can attach to melanin pigments in the skin, which can lead to variations in the effectiveness and availability of these drugs among people with different skin tones.
“Our review indicates that melanin, the pigment that gives color to the skin, has an unexpected attraction to specific drug compounds,” explained Simon Groen, an assistant professor of evolutionary systems biology at the University of California, Riverside, and coauthor of the paper. “The implications of melanin for drug safety and dosing have largely been ignored, raising serious concerns about the effectiveness of standard dosages, given the wide range of skin tones among people.”
According to Groen and coauthor Sophie Zaaijer, who is a consultant and researcher at UC Riverside focusing on diversity, equity, and inclusion (DEI) in preclinical research and clinical trials, the current FDA protocols for toxicity testing do not adequately consider how skin pigmentation impacts drug interactions.
“This oversight is especially troubling against the backdrop of the push for more diverse clinical trials as laid out in the agency’s Diversity Action Plan,” Zaaijer noted. “Yet current practices in early-stage drug development still mainly involve drug testing on white individuals of Northern European descent.”
One example the researchers found involves nicotine’s bond with skin pigments, which may influence smoking behavior among individuals with different skin tones and raises concerns about the effectiveness of nicotine patches for quitting smoking.
“Are we unintentionally shortchanging smokers with darker skin tones who rely on these patches to quit?” Groen questioned.
Groen and Zaaijer recommend a novel approach using human 3D skin models displaying various pigmentation levels, offering pharmaceutical companies an effective way to evaluate drug binding properties on different skin types.
“The factor of skin pigmentation should be factored into safety and dosing calculations,” Zaaijer emphasized. “We are on the verge of a groundbreaking change in the biomedical field, where embracing inclusivity is not just preferable, but essential.”
The researchers point out that skin pigmentation is just a part of the overall picture. Genetic diversity among minority groups can result in significantly different responses to medications across races and ethnicities, affecting up to 20% of all drugs.
“However, our molecular insight into these differences is still quite limited,” Zaaijer stated.
The researchers recognize that changes promoting inclusivity, which include race, ethnicity, sex, and age, require a thorough revision of all FDA guidelines concerning clinical endpoints to align with the FDA’s Diversity Action Plan.
“This is a massive undertaking that will require clear communication between academics, industry researchers, health professionals, and regulators,” Zaaijer said. “The future of medicine depends on our ability to connect these currently separate teams.”
They also note that a shift towards inclusive drug development is imminent, spurred by the new Food and Drug Omnibus Reform Act passed in 2022.
“The FDA recently released their draft guidelines,” Zaaijer mentioned. “Once finalized in a few months, these guidelines will require consideration of patient diversity in clinical trials and preclinical research and development. The next step will be to clarify which pharmacokinetic variables should be evaluated in drug development processes to achieve equitable medications.”
The researchers are keen to inspire both the pharmaceutical sector and academic institutions to begin systematic evaluations in preclinical research regarding skin pigmentation and drug behavior.
Moreover, they urge patients, advocacy groups, and participants in clinical trials to raise questions regarding the efficacy and safety of drugs for specific ancestries, such as asking, “Has this medication been evaluated for safety in people of different ancestral backgrounds, including mine?” They assert that clinicians and pharmaceutical representatives should provide accessible, clear documents summarizing testing outcomes.
They recognize that this goal is challenging given the current drug development landscape.
“Typically, drugs are tested on one or a few human cell models, mainly from donors of Northern European descent,” Zaaijer explained. “These drugs then go through testing in rodent models. If these initial tests are promising, the drug proceeds to clinical trials. But, can we confidently give these drugs to a diverse population if they haven’t been tested, for instance, on human cell models representing various ancestries? Would you jump off a bridge with bungee cords that haven’t been tested for your weight? Probably not. So why is this the standard for drugs?”
Groen highlighted that certain genetic variations are more common in different ancestral backgrounds, which can influence how a drug is processed and functions within the body.
“If drug discovery considers diverse ancestral backgrounds from the beginning, various groups of people may have more confidence in the drug development process and may be more willing to participate in clinical trials because they will be better informed about any associated risks,” he stated.
