Wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of OAT1/3 and P-gp
| Autor: | Ying Li, Cong-Yang Ding, Zhan-Jun Dong, Xiaonan Wang, Ya-Jing Li, Ran Fu, Cai-Hui Guo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Chemistry Cmax Area under the curve General Medicine Drug interaction Pharmacology Small intestine Blot 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Real-time polymerase chain reaction Pharmacokinetics 030220 oncology & carcinogenesis medicine Original Article Methotrexate 030304 developmental biology medicine.drug |
| Zdroj: | Ann Transl Med |
| ISSN: | 2305-5847 2305-5839 |
| DOI: | 10.21037/atm-21-1303 |
| Popis: | BACKGROUND: Methotrexate (MTX) is an important anticancer agent and immunosuppressant with a narrow therapeutic window. Wuzhi capsule (WZC) is an extract of Schisandra which is widely used to treat liver diseases. Co-administration of MTX and WZC is common in the clinical setting, but research on the interaction between WZC and MTX is limited. This study aimed to investigate the effects of WZC on the pharmacokinetics of MTX in rats and to explore the role of membrane transport proteins OAT1/3 and P-gp in the interaction of these drugs. METHODS: Plasma MTX concentration was detected by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS), and the messenger RNA (mRNA) and protein expression of OAT1/3 and P-gp was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting analyses, respectively. RESULTS: The study results revealed that co-administration of WZC decreased the CL(z/F) and V(z/F) of MTX, increased the C(max) and area under the curve [(AUC)(0–24 h)] of MTX, and inhibited OAT1/3 expression in the kidney and P-gp expression in the small intestine. CONCLUSIONS: The findings suggested that there is a drug interaction between WZC and MTX and that OAT1/3 in the kidney and P-gp in the small intestine may be the main targets mediating the drug interaction, and attention should be paid when they are used in combination. |
| Databáze: | OpenAIRE |
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