Abstract / Summary
Abstract Background The cytotoxic drug fluorouracil (5-FU) has long been used to treat breast cancers. This study aims to investigate the association of clinical and pharmacogenetic factors with the pharmacokinetic profile of 5-FU, drug exposure and toxicity profile in breast cancer patients. Methodology: The 200 breast cancer patients taking 5-FU infusion were taken from the Nishtar Hospital's Oncology Department, Multan. Mann-Whitney U tests and multivariate linear regression models were used to evaluate the effect of DPYD and MTHFR gene polymorphism on the pharmacokinetics of 5-FU and drug-induced toxicity. Results Participants who grew up in an urban area had significantly higher AUC 0−t (195.08 µg•h/mL vs. 43.17 µg•h/mL; p < 0.001). Genetic variants are significantly associated with pharmacokinetic parameters. The pharmacokinetic evaluation revealed a mean half-life of 0.25 hours, a clearance rate of 26.37 mg/(µg/ml)/h, a Cmax of 28.08 µg/ml, and an AUC₀–t of 55.33 µg/ml·h. Body mass index showed significant associations with Tmax, Cmax, and AUC₀–t (p < 0.05). Gastrointestinal toxicity, nausea, vomiting, and anemia were associated with genotype-specific dose variability. Conclusion These findings provide strong data-driven evidence to support the integration of clinical characteristics and genetic profiling into personalized dosing and monitoring strategies to optimize efficacy while minimizing adverse effects in breast cancer management.