Question

During clinical trials, fedratinib, a Janus Kinase inhibitor, was found to cause thiamine (Vitamin B1) deficiency in a group of patients. Please indicate which of the following statements is most consistent with this observation? 1. Fedratinib inhibited the efflux pump, P-glycoprotein, which is localized to the apical membrane of the intestine. 2. Fedratinib inhibited the thiamine transporter, THTR2 (SLC19A3), found on the apical membrane of the intestine. 3. Fedratinib stimulated the thiamine transporter, THTR2 (SLC19A3), found on the apical membrane of the intestine. 4. Thiamine inhibited the efflux pump, P-glycoprotein, which is localized to the apical membrane of the intestine. 5. Fedratinib inhibited the active secretion of thiamine in the kidney by MATE1 (SLC47A1).

Answer 1

2.In summary the study was carried out to discern the mechanism underlying fedratinib -induced WE.The results clearly demonstrate that fedratinib is a potent inhibitor of thiamine uptake and transport via specific inhibition of hTHTR2.The other thing to note that is nausea,diarrhoea and vomiting are the major adverse events of Fedratinib and these effects may contribute to exarcerbrate the direct inhibition of thiamine uptske by fedratinib leading to a more pronounced thiamine deficiency.