In Vivo pharmacokinetic interactions of ribociclib with rivaroxaban and apixaban in rats: implications for increased drug exposure and dose adjustments

作者：Zihan Liu, Wenyu Du, Qimin Wang, Zhi Wang, Jing An, Yinling Ma, Zhanjun Dong, Ying Li · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1530806 · 被引用次数：3 · 研究领域：Advanced Breast Cancer Therapies、HER2/EGFR in Cancer Research、Peptidase Inhibition and Analysis

Background Apixaban (API) and rivaroxaban (RIVA) are orally available inhibitors of coagulation factor Xa and are commonly used to treat cancer-related venous thrombosis. Ribociclib (RIBO), a first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR + /HER2 − ) advanced breast cancer, is an inhibitor of CYP3A4, P-gp, and BCRP. Given the potential for these drugs to be co-administered in clinical settings, there is limited information regarding the pharmacokinetic drug-drug interactions (DDIs) between ribociclib and these anticoagulants. This study aimed to evaluate the extent of DDIs between ribociclib and rivaroxaban or apixaban in rats and to explore the optimization of drug dosing strategies. Methods Male Sprague-Dawley rats were divided into 9 groups (n = 6), receiving ribociclib, apixaban, rivaroxaban, ribociclib with rivaroxaban, ribociclib with apixaban, and combinations with reduced doses and time intervals. Blood concentrations were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetic parameters such as AUC, C max , CL z /F, and V z /F. Results Ribociclib significantly increased exposure to both rivaroxaban and apixaban, with a greater impact on rivaroxaban. Specifically, ribociclib increased the AUC 0-t , AUC 0- ∞ and C max of rivaroxaban (normal dose) by about 2.4-fold, 2.1-fold and 1.8-fold, while increasing apixaban exposure by about 60.82%, with a trend ...