Effect of polyethylene glycol 400 on the pharmacokinetics and tissue distribution of baicalin by intravenous injection based on the enzyme activity of UGT1A8/1A9.

Autor: Shang LY; State Key Laboratory of Functions and Applications of Medicinal Plants and School of Pharmacy, Guizhou Medical University, Guiyang 550025, China; Microbiology and Biochemical Pharmaceutical Engineering Research Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 550004, China; Guizhou Medical University Experimental Animal Center, Guizhou Medical University, Guiyang 550025, China., Zhou MH; Inspection Center of Guizhou Drug Administration, Guiyang 550025, China., Cao SY; State Key Laboratory of Functions and Applications of Medicinal Plants and School of Pharmacy, Guizhou Medical University, Guiyang 550025, China; Microbiology and Biochemical Pharmaceutical Engineering Research Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 550004, China; Guizhou Medical University Experimental Animal Center, Guizhou Medical University, Guiyang 550025, China., Zhang M; State Key Laboratory of Functions and Applications of Medicinal Plants and School of Pharmacy, Guizhou Medical University, Guiyang 550025, China; Microbiology and Biochemical Pharmaceutical Engineering Research Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 550004, China; Guizhou Medical University Experimental Animal Center, Guizhou Medical University, Guiyang 550025, China., Wang PJ; State Key Laboratory of Functions and Applications of Medicinal Plants and School of Pharmacy, Guizhou Medical University, Guiyang 550025, China; Microbiology and Biochemical Pharmaceutical Engineering Research Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 550004, China; Guizhou Medical University Experimental Animal Center, Guizhou Medical University, Guiyang 550025, China., Zhang S; State Key Laboratory of Functions and Applications of Medicinal Plants and School of Pharmacy, Guizhou Medical University, Guiyang 550025, China; Microbiology and Biochemical Pharmaceutical Engineering Research Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 550004, China; Guizhou Medical University Experimental Animal Center, Guizhou Medical University, Guiyang 550025, China., Meng XX; State Key Laboratory of Functions and Applications of Medicinal Plants and School of Pharmacy, Guizhou Medical University, Guiyang 550025, China; Microbiology and Biochemical Pharmaceutical Engineering Research Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 550004, China; Guizhou Medical University Experimental Animal Center, Guizhou Medical University, Guiyang 550025, China., Yang QM; State Key Laboratory of Functions and Applications of Medicinal Plants and School of Pharmacy, Guizhou Medical University, Guiyang 550025, China; Microbiology and Biochemical Pharmaceutical Engineering Research Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 550004, China; Guizhou Medical University Experimental Animal Center, Guizhou Medical University, Guiyang 550025, China., Gao XL; State Key Laboratory of Functions and Applications of Medicinal Plants and School of Pharmacy, Guizhou Medical University, Guiyang 550025, China; Microbiology and Biochemical Pharmaceutical Engineering Research Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 550004, China; Guizhou Medical University Experimental Animal Center, Guizhou Medical University, Guiyang 550025, China. Electronic address: gaoxl@gmc.edu.cn.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2023 Jan 01; Vol. 180, pp. 106328. Date of Electronic Publication: 2022 Nov 12.
DOI: 10.1016/j.ejps.2022.106328
Abstrakt: Baicalin (BG) is a bioactive flavonoid extracted from the dried root of the medicinal plant, Scutellaria radix (SR) (dicotyledonous family, Labiatae), and has several biological activities. Polyethylene glycol 400 (PEG400) has been used as a suitable solvent for several traditional Chinese medicines (TCM) and is often used as an excipient for the compound preparation of SR. However, the drug-excipient interactions between BG and PEG400 are still unknown. Herein, we evaluated the effect of a single intravenous PEG400 administration on the BG levels of rats using pharmacokinetic and tissue distribution studies. A liver microsome and recombinant enzyme incubation system were used to further confirm the interaction mechanism between PEG400 and UDP-glucuronosyltransferases (UGTs) (UGT1A8 and UGT1A9). The pharmacokinetic study demonstrated that following the co-intravenous administration of PEG400 and BG, the total clearance (CL z ) of BG in the rat plasma decreased by 101.60% (p < 0.05), whereas the area under the plasma concentration-time curve (AUC) 0-t and AUC 0-inf increased by 144.59% (p < 0.05) and 140.05% (p < 0.05), respectively. Additionally, the tissue distribution study showed that the concentration of BG and baicalein-6-O-β-D-glucuronide (B6G) in the tissues increased, whereas baicalein (B) in the tissues decreased, and the total amount of BG and its metabolites in tissues altered following the intravenous administration of PEG400. We further found that PEG400 induced the UGT1A8 and UGT1A9 enzyme activities by affecting the maximum enzymatic velocity (V max ) and Michaelis-Menten constant (K m ) values of UGT1A8 and UGT1A9. In conclusion, our results demonstrated that PEG400 interaction with UGTs altered the pharmacokinetic behaviors and tissue distribution characteristics of BG and its metabolites in rats.
Competing Interests: Declaration of Competing Interest The authors declare that there are no conflict of interests.
(Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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