Pharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp

Context Rhynchopylline and pellodendrine are major extractions of commonly used Chinese medicine in gynaecology. The interaction between these two compounds could affect treatment efficiency and even result in toxicity during their co-administration in gynaecological prescription. Objective The phar...

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Autores principales:	Qingzhen Meng, Yongheng Cheng, Cui Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	uncaria rhynchophylla (miq.) miq. ex havil phellodendron amurense rupr herb–herb interaction Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/85c039145bdf4eebb152ea6464ddc55d
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spelling	oai:doaj.org-article:85c039145bdf4eebb152ea6464ddc55d2021-11-11T14:23:41ZPharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp1388-02091744-511610.1080/13880209.2021.1999988https://doaj.org/article/85c039145bdf4eebb152ea6464ddc55d2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2021.1999988https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context Rhynchopylline and pellodendrine are major extractions of commonly used Chinese medicine in gynaecology. The interaction between these two compounds could affect treatment efficiency and even result in toxicity during their co-administration in gynaecological prescription. Objective The pharmacokinetic interaction between rhynchopylline and pellodendrine and the potential mechanism were investigated in this study. Materials and methods Sprague-Dawley rats were randomly divided into four groups to investigate the pharmacokinetic interaction between rhynchopylline (30 mg/kg) and pellodendrine (20 mg/kg) with single dose of these two drugs as the control. The transport of rhynchopylline was evaluated in the Caco-2 cell model. Additionally, the metabolic stability and the activity of corresponding CYP450 enzymes were assessed in rat liver microsomes. Results The pharmacokinetic profile of rhynchopylline was dramatically affected by pellodendrine with the increased area under the pharmacokinetic curve (3080.14 ± 454.54 vs. 1728.08 ± 220.598 μg/L*h), Cmax (395.1 ± 18.58 vs. 249.1 ± 16.20 μg/L), prolonged t1/2 (9.74 ± 2.94 vs. 4.81 ± 0.42 h) and the reduced clearance rate (from 11.39 ± 1.37 to 5.67 ± 1.42 L/h/kg). No significant changes were observed in the pharmacokinetics of pellodendrine. The transport of rhynchopylline was significantly inhibited by pellodendrine with a decreasing efflux ratio (1.43 vs. 1.79). Pellodendrine significantly inhibited the activity of CYP1A2 and CYP2C9 with IC50 values of 22.99 and 16.23 μM, which are critical enzymes responsible for the metabolism of rhynchopylline. Discussion and conclusions The adverse interaction between rhynchopylline and pellodendrine draws attention to the co-administration of these two herbs and provides a reference for further investigations with a broader study population.Qingzhen MengYongheng ChengCui ZhouTaylor & Francis Grouparticleuncaria rhynchophylla (miq.) miq. ex havilphellodendron amurense ruprherb–herb interactionTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 59, Iss 1, Pp 1551-1555 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	uncaria rhynchophylla (miq.) miq. ex havil phellodendron amurense rupr herb–herb interaction Therapeutics. Pharmacology RM1-950
spellingShingle	uncaria rhynchophylla (miq.) miq. ex havil phellodendron amurense rupr herb–herb interaction Therapeutics. Pharmacology RM1-950 Qingzhen Meng Yongheng Cheng Cui Zhou Pharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp
description	Context Rhynchopylline and pellodendrine are major extractions of commonly used Chinese medicine in gynaecology. The interaction between these two compounds could affect treatment efficiency and even result in toxicity during their co-administration in gynaecological prescription. Objective The pharmacokinetic interaction between rhynchopylline and pellodendrine and the potential mechanism were investigated in this study. Materials and methods Sprague-Dawley rats were randomly divided into four groups to investigate the pharmacokinetic interaction between rhynchopylline (30 mg/kg) and pellodendrine (20 mg/kg) with single dose of these two drugs as the control. The transport of rhynchopylline was evaluated in the Caco-2 cell model. Additionally, the metabolic stability and the activity of corresponding CYP450 enzymes were assessed in rat liver microsomes. Results The pharmacokinetic profile of rhynchopylline was dramatically affected by pellodendrine with the increased area under the pharmacokinetic curve (3080.14 ± 454.54 vs. 1728.08 ± 220.598 μg/L*h), Cmax (395.1 ± 18.58 vs. 249.1 ± 16.20 μg/L), prolonged t1/2 (9.74 ± 2.94 vs. 4.81 ± 0.42 h) and the reduced clearance rate (from 11.39 ± 1.37 to 5.67 ± 1.42 L/h/kg). No significant changes were observed in the pharmacokinetics of pellodendrine. The transport of rhynchopylline was significantly inhibited by pellodendrine with a decreasing efflux ratio (1.43 vs. 1.79). Pellodendrine significantly inhibited the activity of CYP1A2 and CYP2C9 with IC50 values of 22.99 and 16.23 μM, which are critical enzymes responsible for the metabolism of rhynchopylline. Discussion and conclusions The adverse interaction between rhynchopylline and pellodendrine draws attention to the co-administration of these two herbs and provides a reference for further investigations with a broader study population.
format	article
author	Qingzhen Meng Yongheng Cheng Cui Zhou
author_facet	Qingzhen Meng Yongheng Cheng Cui Zhou
author_sort	Qingzhen Meng
title	Pharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp
title_short	Pharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp
title_full	Pharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp
title_fullStr	Pharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp
title_full_unstemmed	Pharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp
title_sort	pharmacokinetic interaction between rhynchopylline and pellodendrine via cyp450 enzymes and p-gp
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/85c039145bdf4eebb152ea6464ddc55d
work_keys_str_mv	AT qingzhenmeng pharmacokineticinteractionbetweenrhynchopyllineandpellodendrineviacyp450enzymesandpgp AT yonghengcheng pharmacokineticinteractionbetweenrhynchopyllineandpellodendrineviacyp450enzymesandpgp AT cuizhou pharmacokineticinteractionbetweenrhynchopyllineandpellodendrineviacyp450enzymesandpgp
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Pharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp

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