Pharmacokinetics of methotrexate mediated by organic anion transporter 3 in adjuvant induced arthritis rats
10.12092/j.issn.1009-2501.2022.05.004
- Author:
Shu PAN
1
;
Yijin WU
1
;
Sasa ZHANG
1
;
Tingting LUO
1
;
Qin YIN
1
;
Shu PAN
2
;
Sasa ZHANG
2
;
Qin YIN
2
;
Qihai WANG
3
;
Yijin WU
4
Author Information
1. Department of Pharmacy, The Second Affiliated Hospital of Wannan Medical College
2. School of Pharmacy, Southern Anhui Medical College
3. Department of Pharmacy, Anhui College of Traditional Chinese Medicine
4. Research Center of Integrated Traditional Chinese and Western Medicine, Wannan Medical College
- Publication Type:Journal Article
- Keywords:
Excretion;
Methotrexate;
Organic anion transporter 3;
Pharmacokinetics;
Rheumatoid arthritis
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2022;27(5):516-525
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To explore the effects of inflammatory conditions on the pharmacokinetics of methotrexate (MTX) and its related mechanisms. METHODS: The model of adjuvant induced arthritis (AIA) was established. The expression of organic anion transporter 3 (OAT3) in kidney was detected by immunohistochemistry, Western blotting and QPCR. The plasma concentration of MTX was detected by LC-MS/MS, and the pharmacokinetics of MTX after different administration time were compared by isolated rat kidney perfusion, kidney slices, in vitro cell uptake and transport experiments. RESULTS: The expression of OAT3 was significantly increased in the kidneys of AIA rats by immunohistochemistry, Western blotting and QPCR. At the same time, the concentration of MTX was detected by the optimized LC-MS/MS. The results showed that the uptake of MTX in the kidney slices of AIA rats was significantly increased, and Pro could reduce the excretion of MTX by inhibiting OAT3. Furthermore, it was demonstrated in vitro that inflammatory pathology can promote renal excretion of MTX by increasing the expression and functional activity of OAT3.CONCLUSION: Under inflammatory pathological conditions, it can increase the expression of OAT3 in the kidney, enhance its functional activity, accelerate the uptake of MTX by the kidney, and promote the excretion of MTX.
