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Effects of Dextran Sulfate Sodium-Induced Ulcerative Colitis on the Disposition of Tofacitinib in Ratsoa mark
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Publication Year
2022-01-01
Journal
Biomolecules and Therapeutics
Publisher
Korean Society of Applied Pharmacology
Citation
Biomolecules and Therapeutics, Vol.30 No.6, pp.510-519
Keyword
CYP2C11CYP3A1/2Dextran sulfate sodiumPharmacokineticsTofacitinibUlcerative colitis
All Science Classification Codes (ASJC)
BiochemistryMolecular MedicinePharmacologyDrug Discovery
Abstract
Tofacitinib, 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.
ISSN
2005-4483
Language
eng
URI
https://aurora.ajou.ac.kr/handle/2018.oak/33029
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85140893971&origin=inward
DOI
https://doi.org/2-s2.0-85140893971
Journal URL
http://www.biomolther.org/
Type
Article
Funding
This work was supported by Basic Science Research Program (NRF-2021R1A2C1011142) through the National Research Foundation of Korea grant funded by the Ministry of Science and ICT, Republic of Korea.
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