Ajou University repository

Effects of Isosakuranetin on Pharmacokinetic Changes of Tofacitinib in Rats with N-Dimethylnitrosamine-Induced Liver Cirrhosisoa mark
Citations

SCOPUS

7

Citation Export

DC Field Value Language
dc.contributor.authorBae, Sung Hun-
dc.contributor.authorChoi, Hyeon Gyeom-
dc.contributor.authorPark, So Yeon-
dc.contributor.authorChang, Sun Young-
dc.contributor.authorKim, Hyoungsu-
dc.contributor.authorKim, So Hee-
dc.date.issued2022-12-01-
dc.identifier.issn1999-4923-
dc.identifier.urihttps://aurora.ajou.ac.kr/handle/2018.oak/33161-
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85144867040&origin=inward-
dc.description.abstractTofacitinib, a Janus kinase 1 and 3 inhibitor, is used to treat rheumatoid arthritis. It is mainly metabolized by the cytochromes p450 (CYP) 3A1/2 and CYP2C11 in the liver. Chronic inflammation eventually leads to cirrhosis in patients with rheumatoid arthritis. Isosakuranetin (ISN), a component of Citrus aurantium L., has hepatoprotective effects in rats. This study was performed to determine the effects of ISN on the pharmacokinetics of tofacitinib in rats with N-dimethylnitrosamine-induced liver cirrhosis (LC). After intravenous administration of 10 mg/kg tofacitinib to control (CON), LC, and LC treated with ISN (LC-ISN) rats, the total area under the plasma concentration–time curves (AUC) from time zero to infinity increased by 158% in LC rats compared to those in CON rats; however, the AUC of LC-ISN rats decreased by 35.1% compared to that of LC rat. Similar patterns of AUC changes were observed in the LC and LC-ISN rats after oral administration of 20 mg/kg tofacitinib. These results can be attributed to decreased non-renal clearance (CLNR) and intestinal intrinsic clearance (CLint) in the LC rats and increased intestinal and hepatic CLint in the LC-ISN rats. Our findings imply that ISN treatment in LC rats restored the decrease in either CLNR or CLint, or both, through increased hepatic and intestinal expression of CYP3A1/2 and CYP2C11, which is regulated by the induction of pregnane X receptor (PXR) and constitutive androstane receptor (CAR).-
dc.description.sponsorshipThis work was supported by the Basic Science Research Program through a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT) (NRF-2021R1A2C1011142), and the Ministry of Education (NRF-2022R1A6A3A13071621), Korea.-
dc.language.isoeng-
dc.publisherMDPI-
dc.titleEffects of Isosakuranetin on Pharmacokinetic Changes of Tofacitinib in Rats with N-Dimethylnitrosamine-Induced Liver Cirrhosis-
dc.typeArticle-
dc.citation.number12-
dc.citation.titlePharmaceutics-
dc.citation.volume14-
dc.identifier.bibliographicCitationPharmaceutics, Vol.14 No.12-
dc.identifier.doi10.3390/pharmaceutics14122684-
dc.identifier.scopusid2-s2.0-85144867040-
dc.identifier.urlhttp://www.mdpi.com/journal/pharmaceutics-
dc.subject.keywordCAR-
dc.subject.keywordCYP2C11-
dc.subject.keywordCYP3A1/2-
dc.subject.keywordisosakuranetin-
dc.subject.keywordliver cirrhosis-
dc.subject.keywordpharmacokinetics-
dc.subject.keywordPXR-
dc.subject.keywordtofacitinib-
dc.type.otherArticle-
dc.description.isoatrue-
dc.subject.subareaPharmaceutical Science-
Show simple item record

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Chang, Sun-Young Image
Chang, Sun-Young장선영
Division of Pharmacy Sciences
Read More

Total Views & Downloads

File Download

  • There are no files associated with this item.