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

Shang, Le-Yuan; Zhou, Minghao; Cao, Sanxing; Zhang, Min; Wang, Pengjiao; Zhang, Shuo; Meng, Xiao-Xia; Yang, Qimei; Xiuli, Gao

doi:10.1016/j.ejps.2022.106328

Cited by 6 publications

(3 citation statements)

References 54 publications

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“…It is suggested that PEG400 may activate the related phase II metabolic enzymes. A previous study by the group showed that PEG400 had a significant promoting effect on UGT1A8 and UGT1A9 [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Study on the Effect of Pharmaceutical Excipient PEG400 on the Pharmacokinetics of Baicalin in Cells Based on MRP2, MRP3, and BCRP Efflux Transporters

Yang,

Zhang,

Zhao

et al. 2024

Pharmaceutics

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Pharmaceutical excipient PEG400 is a common component of traditional Chinese medicine compound preparations. Studies have demonstrated that pharmaceutical excipients can directly or indirectly influence the disposition process of active drugs in vivo, thereby affecting the bioavailability of drugs. In order to reveal the pharmacokinetic effect of PEG400 on baicalin in hepatocytes and its mechanism, the present study first started with the effect of PEG400 on the metabolic disposition of baicalin at the hepatocyte level, and then the effect of PEG400 on the protein expression of baicalin-related transporters (BCRP, MRP2, and MRP3) was investigated by using western blot; the effect of MDCKII-BCRP, MDCKII-BCRP, MRP2, and MRP3 was investigated by using MDCKII-BCRP, MDCKII-MRP2, and MDCKII-MRP3 cell monolayer models, and membrane vesicles overexpressing specific transporter proteins (BCRP, MRP2, and MRP3), combined with the exocytosis of transporter-specific inhibitors, were used to study the effects of PEG400 on the transporters in order to explore the possible mechanisms of its action. The results demonstrated that PEG400 significantly influenced the concentration of baicalin in hepatocytes, and the AUC0–t of baicalin increased from 75.96 ± 2.57 μg·h/mL to 106.94 ± 2.22 μg·h/mL, 111.97 ± 3.98 μg·h/mL, and 130.42 ± 5.26 μg·h/mL (p ˂ 0.05). Furthermore, the efflux rate of baicalin was significantly reduced in the vesicular transport assay and the MDCKII cell model transport assay, which indicated that PEG400 had a significant inhibitory effect on the corresponding transporters. In conclusion, PEG400 can improve the bioavailability of baicalin to some extent by affecting the efflux transporters and thus the metabolic disposition of baicalin in the liver.

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Section: Discussionmentioning

confidence: 99%

Study on the Effect of Pharmaceutical Excipient PEG400 on the Pharmacokinetics of Baicalin in Cells Based on MRP2, MRP3, and BCRP Efflux Transporters

Yang,

Zhang,

Zhao

et al. 2024

Pharmaceutics

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“…Studies have shown that PEG400 alters the systemic exposure of drugs through multiple pathways, such as drug-metabolizing enzymes and transporter functions, affecting cell membrane microenvironments and reversibly opening tight junctions [5][6][7][8][9]. Our previous study also showed that PEG400 could increase the blood concentration and tissue distribution of baicalin by inducing the activities of UGT1A8 and UGT1A9 [10][11][12]. Furthermore, we found that the long-term application of PEG400 as the matrix for TCM soft capsules can cause diarrhea and weight loss in animals, which reminds us to pay attention to the potential impact on healthy bodies.…”

Section: Introductionmentioning

confidence: 90%

Detrimental Impacts of Pharmaceutical Excipient PEG400 on Gut Microbiota and Metabolome in Healthy Mice

Zhao,

Wang,

Sun

et al. 2023

Molecules

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Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but also facilitates the absorption of multiple drugs. Our previous study found that the long-term application of PEG400 as an adjuvant in traditional Chinese medicine preparations resulted in wasting and weight loss in animals, which aroused our concern. In this study, 16S rRNA high-throughput sequencing technology was used to analyze the diversity of gut microbiota, and LC-MS/MS Q-Exactive Orbtriap metabolomics technology was used to analyze the effect of PEG400 on the metabolome of healthy mice, combined with intestinal pathological analysis, aiming to investigate the effects of PEG400 on healthy mice. These results showed that PEG400 significantly altered the structure of gut microbiota, reduced the richness and diversity of intestinal flora, greatly increased the abundance of Akkermansia muciniphila (A. muciniphila), increased the proportion of Bacteroidetes to Firmicutes, and reduced the abundance of many beneficial bacteria. Moreover, PEG400 changed the characteristics of fecal metabolome in mice and induced disorders in lipid and energy metabolism, thus leading to diarrhea, weight loss, and intestinal inflammation in mice. Collectively, these findings provide new evidence for the potential effect of PEG400 ingestion on a healthy host.

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“…The pharmacokinetic effects of baicalin combined administration show a common feature: baicalin can significantly alter drug pharmacokinetics with the same cytochrome P450 (CYP) enzyme activity or high protein binding [45]. Concretely, the effects of baicalin on phenacetin [46], theophylline [47], midazolam [48], dexamethasone [49,50], nifedipine [51,52], and rosuvastatin [53] involve the metabolism through CYP 1A2, CYP2E1, CYP3A, and CYP2D [47]. Baicalin was also found to alter the pharmacokinetics of nifedipine, another CYP3A substrate, in a different way [54].…”

Section: Interaction Between Baicalin and Other Drugsmentioning

confidence: 99%

The Pharmacological Efficacy of Baicalin in Inflammatory Diseases

Wen

Wang

Zhao

et al. 2023

IJMS

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Baicalin is one of the most abundant flavonoids found in the dried roots of Scutellaria baicalensis Georgi (SBG) belonging to the genus Scutellaria. While baicalin is demonstrated to have anti-inflammatory, antiviral, antitumor, antibacterial, anticonvulsant, antioxidant, hepatoprotective, and neuroprotective effects, its low hydrophilicity and lipophilicity limit the bioavailability and pharmacological functions. Therefore, an in-depth study of baicalin’s bioavailability and pharmacokinetics contributes to laying the theoretical foundation for applied research in disease treatment. In this view, the physicochemical properties and anti-inflammatory activity of baicalin are summarized in terms of bioavailability, drug interaction, and inflammatory conditions.

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

Cited by 6 publications

References 54 publications

Study on the Effect of Pharmaceutical Excipient PEG400 on the Pharmacokinetics of Baicalin in Cells Based on MRP2, MRP3, and BCRP Efflux Transporters

Study on the Effect of Pharmaceutical Excipient PEG400 on the Pharmacokinetics of Baicalin in Cells Based on MRP2, MRP3, and BCRP Efflux Transporters

Detrimental Impacts of Pharmaceutical Excipient PEG400 on Gut Microbiota and Metabolome in Healthy Mice

The Pharmacological Efficacy of Baicalin in Inflammatory Diseases

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