Microplastics and Nanoplastics as Emerging Modifiers of Human Drug Pharmacokinetics: Implications for Adme and Therapeutic Outcomes

Introduction: Microplastics (MPs) and nanoplastics (NPs) are ubiquitous environmental contaminants that may influence human drug pharmacokinetics. Their small size, large surface area, and diverse surface chemistries enable adsorption of drugs, modulation of intestinal barriers, and interactions with metabolic enzymes and transporters, potentially altering absorption, distribution, metabolism, and excretion (ADME). Methods: A comprehensive literature search was performed in PubMed, Scopus, Web of Science, and Google Scholar using keywords including “microplastics,” “nanoplastics,” “ADME,” “pharmacokinetics,” and “drug–particle interactions.” In vitro, in vivo, and human biomonitoring studies, along with relevant physiologically based pharmacokinetic (PBPK) modeling, were reviewed to evaluate mechanistic evidence and clinical implications. Results: Experimental data indicate that MPs/NPs can adsorb drug molecules, disrupt tight junctions, modulate transporter activity (e.g., P-gp, OATP), and alter hepatic enzyme expression (CYP450 isoforms). Nanoplastics can translocate across epithelial barriers, interact with plasma proteins, and accumulate in tissues, affecting systemic drug exposure. Drugs with narrow therapeutic windows—including antiepileptics, anticoagulants, and biologics—are particularly vulnerable. Co-exposure with environmental pollutants such as heavy metals or endocrine disruptors may exacerbate these effects. While mechanistic insights from cellular and animal studies are substantial, human pharmacokinetic evidence remains limited. Conclusion: MPs and NPs represent emerging modulators of drug disposition, with potential consequences for efficacy and safety. Integrating biomonitoring, PBPK modeling, and multi-omics approaches is essential to assess real-world impacts. Recognition of particle-mediated drug interactions is critical for precision pharmacotherapy, regulatory evaluation, and development of mitigation strategies for populations chronically exposed to environmental plastics.