Effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism

Sun, Hongjuan; Wang, Jingfeng; Lv, Juan

doi:10.1080/13880209.2019.1651876

Cited by 18 publications

(17 citation statements)

References 25 publications

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“…P-gp is an important transporter that participates in the transport of various drugs and also plays a vital role in the drug-drug interaction between different types of drugs (Balayssac et al 2005;Aszalos 2007). In the drug-drug interaction between glycyrrhizin and paeoniflorin, the activity of P-gp was also considered as a key factor that mediated the effect of glycyrrhizin on the pharmacokinetics of paeoniflorin (Sun et al 2019). In our study, P-gp was revealed to mediate the transport of paeoniflorin as evidenced by the decreased efflux ratio by verapamil.…”

Section: Discussionmentioning

confidence: 61%

“…P app BA is the apparent permeability coefficient from the BL side to the AP side (cm/s) and P app AB is the apparent permeability coefficient from the AP side to the BL side. involvement of CYP3A4 in the metabolism of paeoniflorin (Sun et al 2019). A previous study has reported that peimine was identified as an inhibitor of CYP3A4 with the IC 50 of 13.43 lM (Li et al 2020).…”

Section: Discussionmentioning

confidence: 97%

“…The therapeutic effect of paeoniflorin has been revealed in a variety of inflammatory disorder models, including rheumatoid arthritis, inflammatory bowel disease, psoriasis and asthma (Zhang et al 2014;Jia and He 2016;Zhou et al 2018). The pharmacokinetics of paeoniflorin could be affected by various drugs, such as glycyrrhizin, during the clinical co-administration (Sun et al 2019).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic interaction between peimine and paeoniflorin in rats and its potential mechanism

Chen

Yin

et al. 2021

Pharmaceutical Biology

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Context: Peimine and paeoniflorin can be combined for the treatment of cough in paediatrics. The interaction during the co-administration could dramatically affect the bioavailability of drugs. Objective: The interaction between peimine and paeoniflorin was investigated in this study. Materials and methods: The pharmacokinetics of paeoniflorin (20 mg/kg) with or without the coadministration of peimine (5 mg/kg for 10 days before paeoniflorin) was orally investigated in Sprague-Dawley rats (n ¼ 6). The group without the peimine was set as the control group. The metabolic stability of paeoniflorin was studied in rat liver with microsomes. The effect of peimine on the absorption of paeoniflorin was investigated with Caco-2 cell monolayers. Results: The C max (244.98 ± 10.95 vs. 139.18 ± 15.14 lg/L) and AUC (0-t) (3295.92 ± 263.02 vs. 139.18 ± 15.14 hÁlg/L) of paeoniflorin was increased by peimine. The t 1/2 was prolonged from 5.33 ± 1.65 to 14.21 ± 4.97 h and the clearance was decreased from 15.43 ± 1.75 to 4.12 ± 0.57 L/h/kg. Consistently, peimine increased the metabolic stability of paeoniflorin with rat liver microsomes with the increased t 1/2 (56.78 ± 2.62 vs. 26.33 ± 3.15 min) and the decreased intrinsic clearance (24.42 ± 3.78 vs. 52.64 ± 4.47 lL/ min/mg protein). Moreover, the transportation of paeoniflorin was also inhibited by peimine as the efflux ratio decreased from 3.06 to 1.63. Discussion and conclusions: Peimine increased the systemic exposure of paeoniflorin through inhibiting the activity of CYP3A4 and P-gp. These results provide a reference for further in vivo studies in a broader population.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic interaction between peimine and paeoniflorin in rats and its potential mechanism

Chen

Yin

et al. 2021

Pharmaceutical Biology

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“…There are several studies investigated the effect of GL on the pharmacokinetics of other drugs got similar results. GL decreased the system exposure of asiatic acid by inducing the activity of CYP450 enzymes (Guo et al 2018), and GL increased the clearance rate of paeoniflorin via inducing the activity of CYP3A4 (Sun et al 2019). The co-administration of GL and celastrol could decrease the plasma concentration of celastrol, due to the enhancement GL exerted on the activity of CYP3A4 (Yan et al 2017).…”

Section: Discussionmentioning

confidence: 98%

“…Next, NBL was orally administered to rats by gavage at a dose of 50 mg/kg. The dosages used in the experiments were based on previous studies (Manthey et al 2011;Guo et al 2018;Sun et al 2019). Blood samples (250 lL) were collected into heparinised tubes via the oculi chorioideae vein at 0.083, 0.33, 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 h after the oral administration of NBL.…”

Section: In Vivo Pharmacokinetic Studymentioning

confidence: 99%

Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism

Wang

Dong

et al. 2020

Pharmaceutical Biology

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Context: Both nobiletin (NBL) and glycyrrhizin (GL) have anti-inflammatory and antitumor properties. These agents may be co-administered in the clinic. However, the drug-drug interaction between them is not clear. Objective: The drug-drug interaction between GL and NBL was investigated, to clarify the effect of GL on the pharmacokinetics of NBL, and its main mechanism. Materials and methods: The pharmacokinetic profiles of oral administration of NBL (50 mg/kg) in Sprague-Dawley rats of two groups with six each, with or without pre-treatment of GL (100 mg/kg/day for 7 days), were investigated. The effects of GL on the metabolic stability and transport of NBL were also investigated through the rat liver microsome and Caco-2 cell transwell models. Results: The results showed that GL significantly decreased the peak plasma concentration (from 1.74 ± 0.15 to 1.12 ± 0.10 lg/mL) and the t 1/2 (7.44 ± 0.65 vs. 5.92 ± 0.68) of NBL, and the intrinsic clearance rate of NBL was increased by the pre-treatment with GL (39.49 ± 2.5 vs. 48.29 ± 3.4 lL/min/mg protein). The Caco-2 cell transwell experiments indicated that GL could increase the efflux ratio of NBL from 1.61 to 2.41. Discussion and conclusion: These results indicated that GL could change the pharmacokinetic profile of NBL, via increasing the metabolism and efflux of NBL in rats. It also suggested that the dose of NBL should be adjusted when co-administrated with GL in the clinic.

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UPLC–MS/MS simultaneous determination of seven active ingredients of Yaobitong capsule in rat plasma and its integrated pharmacokinetic application

Deng

Xiao

et al. 2020

Biomedical Chromatography

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A reliable and sensitive UPLC–MS/MS method was first established and validated for the simultaneous determination of seven active ingredients of Yaobitong capsule in rat plasma: ginsenoside Rg1, ginsenoside Rb1, osthole, tetrahydropalmatine, paeoniflorin, albiflorin, and ferulic acid. And this method was further applied for the integrated pharmacokinetic study of Yaobitong capsule in rats after oral administration. Plasma samples (100 μL) were precipitated with 300 μL of methanol using carbamazepine as internal standard. Chromatographic separation was achieved using an Aquity UPLC BEH C18 column (100 × 2.1 mm, 1.7 μm), with the mobile phase consisting of 0.1% formic acid and acetonitrile. The method was validated using a good linear relationship (r ≥ 0.991), and the lower limit of quantification of the analytes ranged from 0.5 to 40 ng/mL. In the integrated pharmacokinetic study, the weight coefficient was calculated by the ratio of AUC0–∞ of each component to the total AUC0–∞ of the seven active ingredients. The integrated pharmacokinetic parameters Cmax, Tmax, and t1/2 were 81.54 ± 9.62 ng/mL, 1.00 ± 0.21 h, and 3.26 ± 1.14 h, respectively. The integration of pharmacokinetic parameters showed a shorter t1/2 because of fully considering the contribution of the characteristics of each active ingredient to the overall pharmacokinetics.

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Effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism

Cited by 18 publications

References 25 publications

Pharmacokinetic interaction between peimine and paeoniflorin in rats and its potential mechanism

Pharmacokinetic interaction between peimine and paeoniflorin in rats and its potential mechanism

Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism

UPLC–MS/MS simultaneous determination of seven active ingredients of Yaobitong capsule in rat plasma and its integrated pharmacokinetic application

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