Predictive Modeling of Pharmacokinetic Drug–Drug and Herb–Drug Interactions in Oncology: Insights From PBPK Studies
International Journal of Toxicology, cilt.44, sa.5, ss.424-440, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Derleme
- Cilt numarası: 44 Sayı: 5
- Basım Tarihi: 2025
- Doi Numarası: 10.1177/10915818251345116
- Dergi Adı: International Journal of Toxicology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Environment Index, MEDLINE
- Sayfa Sayıları: ss.424-440
- Anahtar Kelimeler: chemotherapy, PBPK modeling, drug-drug interactions, drug-phytochemical interactions, herbal medications, herb-drug interactions
- Boğaziçi Üniversitesi Adresli: Evet
Özet
Physiologically based pharmacokinetic (PBPK) modeling is increasingly used to anticipate, quantify, and strategically manage drug–drug (DDI) and herb–drug (HDI) interactions that can alter the exposure of chemotherapy agents together with co-administered phytochemicals or nutraceuticals. To evaluate current knowledge, we performed a comprehensive Google Scholar search (2003–2024) and selected studies that employed PBPK platforms, reported quantitative validation, and focused on chemotherapy-related interactions. From these reports, key modeling parameters, validation metrics, and clinically relevant outcomes were extracted, and then the information was synthesized to identify common trends. Collectively, the evidence indicates that unintended changes in drug exposure—most often mediated by CYP3A4 inhibition or induction—may modify efficacy, toxicity, and overall anticancer response; nevertheless, PBPK models reproduce these effects with high accuracy, and emerging AI-enhanced approaches promise even finer precision. Accordingly, our synthesis underscores how PBPK modeling can help clinicians forecast interaction risk, individualize dosing, and avert therapeutic failure, especially in polypharmacy settings. Integrating these models into routine oncology practice therefore offers a proactive path toward safer, more personalized chemotherapy and, ultimately, better patient outcomes within an increasingly complex therapeutic landscape.