| Status | 已發表Published |
| Interaction of combined glycyrrhizic acid on the pharmacokinetics and liver toxicity of methotrexate | |
Xiong, S.H.; Xiong, W.; Linghu, K.G.; Liang, H.S.; Chen, Q.L.; Xu, W.; Huang, R.Y.; Xu, W.; Yu, H.
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| 2020-12-01 | |
| Source Publication | Abstracts for 4th International Symposium on Phytochemicals in Medicine and Food
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| Abstract | Methotrexate (MTX) is an FDA-approved folic acid antagonist indicated for the treatment of rheumatoid arthritis and the part of first treatment strategy both in China and overseas. However, serious side effects including gastrointestinal manifestations, bone marrow suppression, liver injure, renal failure have been observed and reported for MTX. Currently, a weekly dosage of MTX for RA treatment is around 20-25 mg in the Western hemisphere, or 16 mg in Japan, or no more than10 mg in China is recommended in clinics to reduce the above-mentioned side effects [1]. However, even the low dose of methotrexate is still not free of the side effects. A small elevation of aminotransferases level is common, thus a continuous monitoring of the serum aminotransferases is needed during the MTX medication. In China, the combination of glycyrrhetinic acid (GA) with MTX has been widely used in clinics to prevent and reduce the hepatic and renal damages caused by MTX. GA has been reported to reduce the MTX-induced hepatotoxicity down-regulating PPARg and Nrf2 [2], and the MTX-induced nephrotoxicity through attenuating oxidative stress and inflammation by upregulating the Nrf2/ARE signaling [3]. Although the clinical benefits of the combinational therapy of GA with MTX are observed, the interaction of GA on the pharmacokinetic properties of MTX is still not reported. In the present study, we investigated the effects of GA on the pharmacokinetic profile of MTX both in vitro and in vivo. The results indicated that GA could increase the intestinal absorption rate of GA through modulating the multidrug resistance‐associated protein-1 (MRP-1) medicated drug efflux. A shorter time (tmax) to reach a higher maximum plasma concentration (Cmax) of MTX were detected for the combinational therapy while comparing to the MTX therapy after the oral administration. The oral bioavailability, as well as the in vivo distribution and elimination of MTX did not significantly altered by GA. Moreover, GA was detected to significantly improve MTX-induced liver damages (serum aminotransferases and histology) in rats. |
| Keyword | Interaction glycyrrhizic acid pharmacokinetics liver toxicity methotrexate |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 60103 |
| Document Type | Conference paper |
| Collection | Institute of Chinese Medical Sciences |
| Corresponding Author | Yu, H. |
| Recommended Citation GB/T 7714 | Xiong, S.H.,Xiong, W.,Linghu, K.G.,et al. Interaction of combined glycyrrhizic acid on the pharmacokinetics and liver toxicity of methotrexate[C], 2020. |
| APA | Xiong, S.H.., Xiong, W.., Linghu, K.G.., Liang, H.S.., Chen, Q.L.., Xu, W.., Huang, R.Y.., Xu, W.., & Yu, H. (2020). Interaction of combined glycyrrhizic acid on the pharmacokinetics and liver toxicity of methotrexate. Abstracts for 4th International Symposium on Phytochemicals in Medicine and Food. |
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