Effect of molecular weight of polyethylene glycol on pharmacokinetics of baicalin
10.16438/j.0513-4870.2020-1688
- VernacularTitle:不同相对分子质量的聚乙二醇对黄芩苷药代动力学的影响
- Author:
Ming-hao ZHOU
1
,
2
;
Min ZHANG
1
;
Shuo ZHANG
3
;
Peng-jiao WANG
1
;
Xiao-xia MENG
1
,
2
;
Si-yuan CAO
1
,
2
;
Qi-mei YANG
1
,
2
;
Xiu-li GAO
1
,
2
Author Information
1. State Key Laboratory of Functions and Applications of Medicinal Plants and School of Pharmacy, Guizhou Medical University, Guiyang 550025, China
2. Center of Microbiology and Biochemical Pharmaceutical Engineering, Guizhou Medical University, Guiyang 550025, China
3. Experimental Animal Center of Guizhou Medical University, Guiyang 550025, China
- Publication Type:Research Article
- Keywords:
polyethylene glycol;
baicalin;
baicalein 6-O-β-D-glucuronide;
uridine diphosphate glucuronosyl-transferases 1A8;
uridine diphosphate glucuronosyl-transferases 1A9;
pharmacokinetics
- From:
Acta Pharmaceutica Sinica
2021;56(5):1416-1423
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study was to investigate the effects of polyethylene glycol (PEGs) with different molecular weights (MW: 400, 1 000, 4 000) on the pharmacokinetics of baicalin, and preliminarily analyze its mechanism. Rats were gavaged with baicalin (168 mg·kg-1) + aqueous solution or baicalin + PEGs solution and plasma samples were collected from 0 to 24 h after administration. The concentration of baicalin and its main metabolite baicalein 6-O-β-D-glucuronide (B6G) were determined at different time points by UPLC-MS/MS, and the pharmacokinetic parameters were calculated with DAS 3.0 software. The results showed that PEGs with different molecular weights could effectively increase the AUC0-t of baicalin and B6G, increase the Cmax, and prolong the t1/2, effectively increasing the concentration of baicalin and B6G in vivo. The mechanism may be by promoting the activity of uridine diphosphate glucuronosyl-transferases 1A8 (UGT1A8) and 1A9 (UGT1A9), thereby increasing the transformation rate of baicalin and B6G. The rate of metabolism of B6G was faster than that of baicalin, suggesting that PEGs had a higher affinity for UGT1A8, and PEG400 had the most significant effect. The purpose of this study was to provide a basis for the clinical safe use of baicalin and other flavonoids and the design of new dosage forms with the participation of PEGs. The animal experiment protocol in this study was approved by the Experimental Animal Ethics Committee of Guizhou Medical University.
