Pharmacokinetics and Pharmacodynamics of Natural Products in Oncology: Bridging the Gap between Promise and Clinical Reality

Introduction: Natural products have historically contributed to cancer therapeutics, leading to agents like paclitaxel and vincristine. Recently, compounds such as curcumin, resveratrol, quercetin, and berberine have gained attention due to their multitargeted mechanisms and favorable safety profiles. However, their clinical application remains limited owing to significant pharmacokinetic (PK) and pharmacodynamic (PD) challenges. This review aims to highlight these limitations and explore emerging strategies to enhance their oncotherapeutic potential. Methods: A comprehensive literature review was conducted using peer-reviewed articles and clinical trial reports from databases including PubMed, Scopus, and Web of Science. Key PK/PD limitations and advanced formulation approaches were identified and critically analyzed. Results: Major PK barriers include poor oral bioavailability, low solubility, rapid metabolism, and short half-life. PD challenges involve multi-target effects, inconsistent doseresponse relationships, and a lack of validated biomarkers. Examples include curcumin’s poor bioavailability and resveratrol’s rapid metabolism. Emerging strategies such as nanotechnology-based delivery systems, prodrug development, structural modifications, and co-administration with bioavailability enhancers, such as piperine, have shown promise. Success stories such as Abraxane® (albumin-bound paclitaxel) and topotecan (a camptothecin derivative) illustrate effective translational approaches. Discussion: Overcoming PK/PD limitations is essential for translating natural compounds into effective oncotherapeutics. Integrating nanomedicine, chemical modifications, and bioenhancers improves pharmacological profiles. Conclusion: Future directions should combine pharmacogenomics, nanotechnology, and AI-driven drug discovery to enhance the clinical relevance of natural anticancer agents. For example, AI-guided structural optimization of camptothecin analogs (e.g., topotecan) and nanoparticle-based formulations such as Abraxane® demonstrate how computational and translational innovations can successfully advance natural products into clinical oncology.