Beyond the Basics: Exploring Pharmacokinetic Interactions and Safety in Tyrosine-Kinase Inhibitor Oral Therapy for Solid Tumors

超越基础:探索酪氨酸激酶抑制剂口服治疗实体瘤的药代动力学相互作用和安全性

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Abstract

Cancer remains a major global health burden driven by complex biological mechanisms, and while targeted therapies like tyrosine kinase inhibitors (TKIs) have revolutionized treatment, their efficacy and safety are significantly influenced by drug-drug interactions (DDIs). Tyrosine-kinase receptors (RTKs) regulate critical cellular processes, and their dysregulation through mutations or overexpression drives oncogenesis, with TKIs designed to inhibit these aberrant signaling pathways by targeting RTK phosphorylation. Pharmacokinetic DDIs can critically impact the efficacy and safety of TKIs such as erlotinib, gefitinib, and pazopanib by affecting their absorption, distribution, and metabolism. The modification of pH can influence drug absorption; furthermore, the inhibition or induction of metabolizing enzymes may affect biotransformation, while distribution can be altered through the modulation of transmembrane transporters. Additionally, ensuring quality of life during TKI treatment requires vigilant monitoring and management of adverse events, which range from mild (e.g., rash, diarrhea, fatigue) to severe (e.g., hepatotoxicity, cardiotoxicity). Drug-specific toxicities, such as hyperlipidemia with lorlatinib or visual disturbances with crizotinib, must be assessed using specific criteria, with dose adjustments and supportive care tailored to individual patient responses. Thus, optimal TKI therapy relies on managing drug interactions through multidisciplinary care, monitoring, and patient education to ensure safety and treatment efficacy.

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