The pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro

Context The interaction between nobiletin and anemarsaponin BII could affect the pharmacological activity of these two drugs during their combination. Objective The co-administration of nobiletin and anemarsaponin BII was investigated to explore the interaction and the potential mechanism. Materials...

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Autores principales:	Jie Zhang, Meiling Fan, Xia Yu, Bin Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	paediatric traditional chinese medicine herb–herb interaction cyp3a4 p-gp Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/17bcbbf4bfe945a0b46f29e3ba5cfa37
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spelling	oai:doaj.org-article:17bcbbf4bfe945a0b46f29e3ba5cfa372021-11-04T15:00:41ZThe pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro1388-02091744-511610.1080/13880209.2021.1990355https://doaj.org/article/17bcbbf4bfe945a0b46f29e3ba5cfa372021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2021.1990355https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context The interaction between nobiletin and anemarsaponin BII could affect the pharmacological activity of these two drugs during their combination. Objective The co-administration of nobiletin and anemarsaponin BII was investigated to explore the interaction and the potential mechanism. Materials and methods Male Sprague-Dawley rats were only orally administrated with 50 mg/kg nobiletin as the control and another six rats were pre-treated with 100 mg/kg anemarsaponin BII for 7 d followed by the administration of nobiletin. The transport and metabolic stability of nobiletin were evaluated in vitro, and the effect of anemarsaponin BII on the activity of CYP3A4 was also assessed to explore the potential mechanism underlying the interaction. Results The increasing Cmax (2309.67 ± 68.06 μg/L vs. 1767.67 ± 68.86 μg/L), AUC (28.84 ± 1.34 mg/L × h vs. 19.57 ± 2.76 mg/L × h), prolonged t1/2 (9.80 ± 2.33 h vs. 6.24 ± 1.53 h), and decreased clearance rate (1.46 ± 0.26 vs. 2.42 ± 0.40) of nobilein was observed in rats. Anemarsaponin BII significantly enhanced the metabolic stability of nobiletin in rat liver microsomes (half-life increased from 31.56 min to 39.44 min) and suppressed the transport of nobiletin in Caco-2 cells (efflux rate decreased from 1.57 ± 0.04 to 1.30 ± 0.03). The inhibitory effect of anemarsaponin BII on CYP3A4 was also found with an IC50 value of 10.23 μM. Discussion and conclusions The interaction between anemarsaponin BII and nobiletin was induced by the inhibition of CYP3A4, which should draw special attention in their clinical co-administration.Jie ZhangMeiling FanXia YuBin ZhangTaylor & Francis Grouparticlepaediatrictraditional chinese medicineherb–herb interactioncyp3a4p-gpTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 59, Iss 1, Pp 1528-1532 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	paediatric traditional chinese medicine herb–herb interaction cyp3a4 p-gp Therapeutics. Pharmacology RM1-950
spellingShingle	paediatric traditional chinese medicine herb–herb interaction cyp3a4 p-gp Therapeutics. Pharmacology RM1-950 Jie Zhang Meiling Fan Xia Yu Bin Zhang The pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro
description	Context The interaction between nobiletin and anemarsaponin BII could affect the pharmacological activity of these two drugs during their combination. Objective The co-administration of nobiletin and anemarsaponin BII was investigated to explore the interaction and the potential mechanism. Materials and methods Male Sprague-Dawley rats were only orally administrated with 50 mg/kg nobiletin as the control and another six rats were pre-treated with 100 mg/kg anemarsaponin BII for 7 d followed by the administration of nobiletin. The transport and metabolic stability of nobiletin were evaluated in vitro, and the effect of anemarsaponin BII on the activity of CYP3A4 was also assessed to explore the potential mechanism underlying the interaction. Results The increasing Cmax (2309.67 ± 68.06 μg/L vs. 1767.67 ± 68.86 μg/L), AUC (28.84 ± 1.34 mg/L × h vs. 19.57 ± 2.76 mg/L × h), prolonged t1/2 (9.80 ± 2.33 h vs. 6.24 ± 1.53 h), and decreased clearance rate (1.46 ± 0.26 vs. 2.42 ± 0.40) of nobilein was observed in rats. Anemarsaponin BII significantly enhanced the metabolic stability of nobiletin in rat liver microsomes (half-life increased from 31.56 min to 39.44 min) and suppressed the transport of nobiletin in Caco-2 cells (efflux rate decreased from 1.57 ± 0.04 to 1.30 ± 0.03). The inhibitory effect of anemarsaponin BII on CYP3A4 was also found with an IC50 value of 10.23 μM. Discussion and conclusions The interaction between anemarsaponin BII and nobiletin was induced by the inhibition of CYP3A4, which should draw special attention in their clinical co-administration.
format	article
author	Jie Zhang Meiling Fan Xia Yu Bin Zhang
author_facet	Jie Zhang Meiling Fan Xia Yu Bin Zhang
author_sort	Jie Zhang
title	The pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro
title_short	The pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro
title_full	The pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro
title_fullStr	The pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro
title_full_unstemmed	The pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro
title_sort	pharmacokinetic study on the interaction between nobiletin and anemarsaponin bii in vivo and in vitro
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/17bcbbf4bfe945a0b46f29e3ba5cfa37
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The pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro

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