ArticleDrug design, development and therapy2025
In vivo Pharmacokinetic Interactions Between Palbociclib and Rivaroxaban or Apixaban: Implications for Increased Drug Exposure and Dose Adjustments.
Article in Drug design, development and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Apixaban and rivaroxaban are oral direct factor Xa inhibitors, primarily eliminated through CYP3A4-mediated metabolism and direct intestinal excretion. Previous studies suggest that palbociclib, a CDK4/6 inhibitor, may increase the systemic exposure of these anticoagulants; however, the specific pharmacokinetic mechanisms remain unclear. This study aims to evaluate the effects of palbociclib on the pharmacokinetics of apixaban and rivaroxaban using a rat model to optimize combined drug regimens. Methods: Male Sprague-Dawley rats were divided into eleven groups to assess interactions between palbociclib and either apixaban or rivaroxaban (n=6). Rats received single or combined doses of palbociclib (11 mg/kg), apixaban (0.25 or 0.5 mg/kg), or rivaroxaban (1 or 2 mg/kg), administered either simultaneously or with a 12-hour interval. Plasma drug concentrations were measured at multiple time points using UPLC-MS/MS, and pharmacokinetic parameters (AUC, C Results: The results demonstrated that palbociclib significantly increased the exposure of both apixaban and rivaroxaban. Specifically, palbociclib elevated the AUC and C Conclusion: The remarkable increased exposure of DOAC suggest that palbociclib likely enhance intestinal absorption mediated by decreased P-gp and BCRP expression, indicating markedly improved bioavailability for both drugs. These pharmacokinetic interactions provide valuable insights for optimizing dosing regimens of palbociclib in combination with apixaban or rivaroxaban, potentially reducing toxicity risks and enhancing the safety of co-administration in clinical settings.
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