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To determine the effects of CP\u201025 on the pharmacokinetics of LEF in rats, we developed a ultra\u2010high performance liquid chromatography\u2010tandem mass spectrometry (UPLC\u2010MS\/MS)\u2010based method for the determination of levels of teriflunomide (TER, an active metabolite of LEF). This method was used to determine TER concentrations in the plasma, urine, faeces and bile; heart, liver, spleen, lung, kidney, intestinal, brain and synovial tissues; and peripheral blood mononuclear cells (PBMCs) of rats in the control (LEF [10\u00a0mg\/kg]) and combined (CP\u201025 [50\u2009mg\/kg\u2009\u00d7\u20097d] plus LEF [10\u00a0mg\/kg]) groups. TER area under the curve [AUC], <jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub>, mean residence time (MRT), <jats:italic>t<\/jats:italic><jats:sub>1\/2\u03b1<\/jats:sub> and <jats:italic>t<\/jats:italic><jats:sub>1\/2\u03b2<\/jats:sub> were significantly lower, and clearance (CL) was significantly higher in the combined group than in the control group. Oral CP\u201025 administration in combination with LEF was found to promote TER excretion in urine, faeces and bile and to reduce its contents in most tissues and organs, especially in the liver, which may reduce LEF\u2010induced liver injury. CP\u201025 also increased TER exposure in the synovium and its absorption by PBMCs, and this could explain the synergistic effects of CP\u201025 and LEF.<\/jats:p>","DOI":"10.1111\/bcpt.13685","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T16:06:28Z","timestamp":1637251588000},"page":"364-374","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of paeoniflorin\u20106\u2032\u2010O\u2010benzene sulfonate on the pharmacokinetics, excretion and tissue distribution of leflunomide in rats"],"prefix":"10.1111","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0068-2825","authenticated-orcid":false,"given":"Ning","family":"Xiao","sequence":"first","affiliation":[{"name":"Institute of Clinical Pharmacology, Key Laboratory of Anti\u2010inflammatory and Immune Medicine, Ministry of Education, Anti\u2010inflammatory Immune Drugs Collaborative Innovation Center Anhui 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