Pharmacokinetic profiling of the bioactive components of Sijunzi Decoction in a rat model of breast cancer: Insights into herb-drug interactions with cyclophosphamide.

Abstract

This study investigated the pharmacokinetics of Sijunzi Decoction (SJZD) components and their interactions with cyclophosphamide (CTX) in breast cancer (BC) rats. The BC model was induced using 7,12-dimethylbenz[a]anthracene (DMBA). Using UPLC-Orbitrap-MS/MS, we identified 23 SJZD-derived compounds in rat plasma. Subsequently, a validated UPLC-TQ-MS/MS method was developed to quantify seven bioactive analytes. Compared with normal rats, BC model rats exhibited significantly altered pharmacokinetics: ginsenosides Rb1 and Rc showed enhanced systemic exposure and prolonged elimination, whereas the clearance of glycyrrhetinic acid was accelerated. Co-administration with CTX further increased the absorption of ginsenosides but markedly reduced the exposure and accelerated the clearance of licorice-derived compounds (liquiritin, isoliquiritigenin, formononetin, and glycyrrhetinic acid). These findings indicate that breast cancer pathology significantly alters the in vivo disposition of SJZD components, and that CTX induces complex herb-drug interactions. This study provides a critical pharmacokinetic basis for the rational clinical application of SJZD as an adjuvant therapy in breast cancer patients, particularly when combined with chemotherapy.