Effects of paeoniflorin-6′-O-benzene sulfonate on the pharmacokinetics, excretion and tissue distribution of leflunomide in rats
Ning Xiao
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorFeng Xiao
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorJinzhang Gao
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorZhengkun Xu
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorQianlei Wang
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorJiajie Kuai
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorCorresponding Author
Wei Wei
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Correspondence
Wei Wei and Chun Wang, Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, Anhui 230032, China.
Email: [email protected];[email protected]
Search for more papers by this authorCorresponding Author
Chun Wang
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Correspondence
Wei Wei and Chun Wang, Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, Anhui 230032, China.
Email: [email protected];[email protected]
Search for more papers by this authorNing Xiao
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorFeng Xiao
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorJinzhang Gao
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorZhengkun Xu
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorQianlei Wang
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorJiajie Kuai
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Search for more papers by this authorCorresponding Author
Wei Wei
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Correspondence
Wei Wei and Chun Wang, Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, Anhui 230032, China.
Email: [email protected];[email protected]
Search for more papers by this authorCorresponding Author
Chun Wang
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, China
Correspondence
Wei Wei and Chun Wang, Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Medical University, Hefei, Anhui 230032, China.
Email: [email protected];[email protected]
Search for more papers by this authorNing Xiao and Feng Xiao contributed equally to this work.
Funding information: Project for Basic and Clinical Cooperative Research in Anhui Medical University, Grant/Award Number: 2019xkjT016; Key Projects of Anhui Province University Outstanding Youth Talent Support Program, Grant/Award Number: gxyqZD2019017; Natural Science Foundation of Anhui Province, Grant/Award Number: 2008085QH402; National Natural Science Foundation of China, Grant/Award Number: 81973332
Abstract
Paeoniflorin-6′-O-benzene sulfonate (CP-25) is a novel ester derivative of paeoniflorin, which has been shown to have synergistic pharmacodynamic effects with leflunomide (LEF). To determine the effects of CP-25 on the pharmacokinetics of LEF in rats, we developed a ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based 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 mg/kg]) and combined (CP-25 [50 mg/kg × 7d] plus LEF [10 mg/kg]) groups. TER area under the curve [AUC], Tmax, mean residence time (MRT), t1/2α and t1/2β were significantly lower, and clearance (CL) was significantly higher in the combined group than in the control group. Oral CP-25 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-induced liver injury. CP-25 also increased TER exposure in the synovium and its absorption by PBMCs, and this could explain the synergistic effects of CP-25 and LEF.
CONFLICT OF INTEREST
The author reports no conflicts of interest in this work.
Supporting Information
| Filename | Description |
|---|---|
| bcpt13685-sup-0001-Supporting Information.docxWord 2007 document , 833.4 KB |
Table 1S The elution gradient of Samples. Table 2S The optimized parameters for TER and IS. Figure 1S Linearity of TER in plasma samples. X represents the concentration of TER (μg/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 2S Linearity of TER in faeces samples. X represents the concentration of TER (ng/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 3S Linearity of TER in urine samples. X represents the concentration of TER (ng/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 4S Linearity of TER in bile samples. X represents the concentration of TER (μg/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 5S Linearity of TER in heart samples. X represents the concentration of TER (ng/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 6S Linearity of TER in liver samples. X represents the concentration of TER (μg/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 7S Linearity of TER in spleen samples. X represents the concentration of TER (ng/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 8S Linearity of TER in lung samples. X represents the concentration of TER (ng/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 9S Linearity of TER in kidney samples. X represents the concentration of TER (μg/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 10S Linearity of TER in intestine samples. X represents the concentration of TER (μg/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 11S Linearity of TER in brain samples. X represents the concentration of TER (ng/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 12S Linearity of TER in synovium samples. X represents the concentration of TER (ng/mL), and Y represents the ratio of the peak area of TER to the peak area of IS. Figure 13S Linearity of TER in PBMC samples. X represents the concentration of TER (ng/mL), and Y represents peak area of TER. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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