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

Context: Paeoniflorin is reported to possess numerous pharmacological activities. Paeoniflorin and glycyrrhizin are always used together for the treatment of disease in China clinics; however, the drug–drug interaction between glycyrrhizin and paeoniflorin is still unknown. Objective: This study inv...

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Autores principales:	Hongjuan Sun, Jingfeng Wang, Juan Lv
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	p-gp cyp450 drug–drug interaction Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/58e3dc65b6694d60923aa572281fa23f
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spelling	oai:doaj.org-article:58e3dc65b6694d60923aa572281fa23f2021-11-17T14:21:56ZEffects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism1388-02091744-511610.1080/13880209.2019.1651876https://doaj.org/article/58e3dc65b6694d60923aa572281fa23f2019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1651876https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Paeoniflorin is reported to possess numerous pharmacological activities. Paeoniflorin and glycyrrhizin are always used together for the treatment of disease in China clinics; however, the drug–drug interaction between glycyrrhizin and paeoniflorin is still unknown. Objective: This study investigates the effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats. Materials and methods: The pharmacokinetics of orally administered paeoniflorin (20 mg/kg) with or without glycyrrhizin pre-treatment (at a dose of 100 mg/kg/day for 7 days) were investigated in male Sprague–Dawley rats using LC-MS/MS. Additionally, Caco-2 cell transwell model and rat liver microsome incubation experiments were also conducted to investigate its potential mechanism. Results: The results showed that when the rats were pre-treated with glycyrrhizin, the Cmax of paeoniflorin decreased from 59.57 ± 10.24 to 45.36 ± 8.61 ng/mL, and AUC0-inf also decreased from 282.02 ± 35.06 to 202.29 ± 28.28 μg·h/L. The t1/2 value of paeoniflorin decreased from 8.48 ± 2.01 to 5.88 ± 1.15 h (p < 0.05). The Caco-2 cell transwell experiments indicated that glycyrrhizin could increase the efflux ratio of paeoniflorin from 2.71 to 3.52, and the rat liver microsome incubation experiments showed that glycyrrhizin could significantly increase its intrinsic clearance rate from 53.7 ± 4.6 to 85.6 ± 7.1 μL/min/mg protein. Conclusions: These results indicated that glycyrrhizin could affect the pharmacokinetics of paeoniflorin, and it might work through decreasing the absorption of paeoniflorin by inducing the activity of P-gp or through increasing the clearance rate in rat liver by inducing the activity of CYP450 enzyme.Hongjuan SunJingfeng WangJuan LvTaylor & Francis Grouparticlep-gpcyp450drug–drug interactionTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 550-554 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	p-gp cyp450 drug–drug interaction Therapeutics. Pharmacology RM1-950
spellingShingle	p-gp cyp450 drug–drug interaction Therapeutics. Pharmacology RM1-950 Hongjuan Sun Jingfeng Wang Juan Lv Effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism
description	Context: Paeoniflorin is reported to possess numerous pharmacological activities. Paeoniflorin and glycyrrhizin are always used together for the treatment of disease in China clinics; however, the drug–drug interaction between glycyrrhizin and paeoniflorin is still unknown. Objective: This study investigates the effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats. Materials and methods: The pharmacokinetics of orally administered paeoniflorin (20 mg/kg) with or without glycyrrhizin pre-treatment (at a dose of 100 mg/kg/day for 7 days) were investigated in male Sprague–Dawley rats using LC-MS/MS. Additionally, Caco-2 cell transwell model and rat liver microsome incubation experiments were also conducted to investigate its potential mechanism. Results: The results showed that when the rats were pre-treated with glycyrrhizin, the Cmax of paeoniflorin decreased from 59.57 ± 10.24 to 45.36 ± 8.61 ng/mL, and AUC0-inf also decreased from 282.02 ± 35.06 to 202.29 ± 28.28 μg·h/L. The t1/2 value of paeoniflorin decreased from 8.48 ± 2.01 to 5.88 ± 1.15 h (p < 0.05). The Caco-2 cell transwell experiments indicated that glycyrrhizin could increase the efflux ratio of paeoniflorin from 2.71 to 3.52, and the rat liver microsome incubation experiments showed that glycyrrhizin could significantly increase its intrinsic clearance rate from 53.7 ± 4.6 to 85.6 ± 7.1 μL/min/mg protein. Conclusions: These results indicated that glycyrrhizin could affect the pharmacokinetics of paeoniflorin, and it might work through decreasing the absorption of paeoniflorin by inducing the activity of P-gp or through increasing the clearance rate in rat liver by inducing the activity of CYP450 enzyme.
format	article
author	Hongjuan Sun Jingfeng Wang Juan Lv
author_facet	Hongjuan Sun Jingfeng Wang Juan Lv
author_sort	Hongjuan Sun
title	Effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism
title_short	Effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism
title_full	Effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism
title_fullStr	Effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism
title_full_unstemmed	Effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism
title_sort	effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/58e3dc65b6694d60923aa572281fa23f
work_keys_str_mv	AT hongjuansun effectsofglycyrrhizinonthepharmacokineticsofpaeoniflorininratsanditspotentialmechanism AT jingfengwang effectsofglycyrrhizinonthepharmacokineticsofpaeoniflorininratsanditspotentialmechanism AT juanlv effectsofglycyrrhizinonthepharmacokineticsofpaeoniflorininratsanditspotentialmechanism
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Effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism

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