Cyclosporine exposure in presence of hetrombopag

The term 'Cyclosporine exposure in presence of hetrombopag' refers to a clinical pharmacokinetic scenario or drug-drug interaction (DDI) study rather than a specific biological target. Cyclosporine is a potent immunosuppressant used to prevent graft rejection and treat autoimmune disorders like severe aplastic anemia by inhibiting the phosphatase activity of calcineurin (PMID: 2545524). Hetrombopag is an orally active, small-molecule thrombopoietin receptor (TPO-R) agonist developed to treat thrombocytopenia by mimicking the action of endogenous thrombopoietin (PMID: 34143365). In clinical settings where these drugs are co-administered, such as in the treatment of aplastic anemia, it is critical to evaluate how hetrombopag affects the systemic exposure of cyclosporine to ensure safety and efficacy. Cyclosporine itself is a well-known inhibitor of various drug transporters, including P-glycoprotein and OATP1B1/1B3, and its own metabolism is sensitive to changes in enzyme and transporter activity (PMID: 33400314). Monitoring the exposure (AUC and Cmax) of cyclosporine is essential because of its narrow therapeutic window and the potential for significant toxicity if levels become elevated.

Other names

Cyclosporine-hetrombopag drug-drug interactionPharmacokinetics of cyclosporine with hetrombopagCyclosporine exposure assessment

Cyclosporine is a calcineurin inhibitor that binds to cyclophilin to inhibit T-cell activation (PMID: 2545524). Hetrombopag is a small-molecule thrombopoietin receptor (TPO-R) agonist that activates the JAK2/STAT signaling pathway to stimulate megakaryocyte proliferation (PMID: 30155755). The interaction between them typically involves the inhibition of transporters like OATP1B1, OATP1B3, and P-glycoprotein by cyclosporine, which can increase the systemic exposure of co-administered drugs like hetrombopag (PMID: 33400314).