PubMed:35811297 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/35811297","sourcedb":"PubMed","sourceid":"35811297","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/35811297","text":"Effects of Dextran Sulfate Sodium-Induced Ulcerative Colitis on the Disposition of Tofacitinib in Rats.\nTofacitinib, a Janus kinase 1 and 3 inhibitor, is mainly metabolized by CYP3A1/2 and CYP2C11 in the liver. The drug has been approved for the chronic treatment of severe ulcerative colitis, a chronic inflammatory bowel disease. This study investigated the pharmacokinetics of tofacitinib in rats with dextran sulfate sodium (DSS)-induced ulcerative colitis. After 1-min of intravenous infusion of tofacitinib (10 mg/kg), the area under the plasma concentration-time curves from time zero to time infinity (AUC) of tofacitinib significantly increased by 92.3%. The time-averaged total body clearance decreased significantly by 47.7% in DSS rats compared with control rats. After the oral administration of tofacitinib (20 mg/kg), the AUC increased by 85.5% in DSS rats. These results could be due to decreased intrinsic clearance of the drug caused by the reduction of CYP3A1/2 and CYP2C11 in the liver and intestine of DSS rats. In conclusion, ulcerative colitis inhibited CYP3A1/2 and CYP2C11 in the liver and intestines of DSS rats and slowed the metabolism of tofacitinib, resulting in increased plasma concentrations of tofacitinib in DSS rats.","tracks":[{"project":"UCDIT_TEST","denotations":[{"id":"T1","span":{"begin":119,"end":133},"obj":"GeneOrGeneProduct"},{"id":"T2","span":{"begin":176,"end":184},"obj":"GeneOrGeneProduct"},{"id":"T3","span":{"begin":972,"end":980},"obj":"GeneOrGeneProduct"},{"id":"T4","span":{"begin":1077,"end":1085},"obj":"GeneOrGeneProduct"}],"attributes":[{"subj":"T1","pred":"source","obj":"UCDIT_TEST"},{"subj":"T2","pred":"source","obj":"UCDIT_TEST"},{"subj":"T3","pred":"source","obj":"UCDIT_TEST"},{"subj":"T4","pred":"source","obj":"UCDIT_TEST"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"UCDIT_TEST","color":"#93ecae","default":true}]}]}}