Influence of verapamil on the pharmacokinetics of oridonin in rats

Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still u...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jing Liu, Ning Zhang, Na Li, Xiaocheng Fan, Ying Li
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	cyp3a4 p-gp drug–drug interaction Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/4e27aaa791904179aeb0edeac67b4784
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4e27aaa791904179aeb0edeac67b4784
record_format	dspace
spelling	oai:doaj.org-article:4e27aaa791904179aeb0edeac67b47842021-11-17T14:21:56ZInfluence of verapamil on the pharmacokinetics of oridonin in rats1388-02091744-511610.1080/13880209.2019.1688844https://doaj.org/article/4e27aaa791904179aeb0edeac67b47842019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1688844https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still unclear. Objective: This study investigated the effect of verapamil on the pharmacokinetics of oridonin in rats and clarified its main mechanism. Materials and methods: The pharmacokinetic profiles of oral administration of oridonin (20 mg/kg) in Sprague-Dawley rats with two groups of six animals each, with or without pre-treatment of verapamil (10 mg/kg/day for 7 days) were investigated. The effects of verapamil on the transport and metabolic stability of oridonin were also investigated using Caco-2 cell transwell model and rat liver microsomes. Results: The results showed that verapamil could significantly increase the peak plasma concentration (from 146.9 ± 10.17 to 193.97 ± 10.53 ng/mL), and decrease the oral clearance (from 14.69 ± 4.42 to 8.09 ± 3.03 L/h/kg) of oridonin. The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of oridonin from 1.67 to 1.15, and the intrinsic clearance rate of oridonin was decreased by the pre-treatment with verapamil (40.06 ± 2.5 vs. 36.09 ± 3.7 µL/min/mg protein). Discussion and conclusions: These results indicated that verapamil could significantly change the pharmacokinetic profile of oridonin in rats, and it might exert these effects through increasing the absorption of oridonin by inhibiting the activity of P-gp, or through inhibiting the metabolism of oridonin in rat liver. In addition, the potential drug–drug interaction should be given special attention when verapamil is used with oridonin. Also, the dose of oridonin should be carefully selected in the clinic.Jing LiuNing ZhangNa LiXiaocheng FanYing LiTaylor & Francis Grouparticlecyp3a4p-gpdrug–drug interactionTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 787-791 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cyp3a4 p-gp drug–drug interaction Therapeutics. Pharmacology RM1-950
spellingShingle	cyp3a4 p-gp drug–drug interaction Therapeutics. Pharmacology RM1-950 Jing Liu Ning Zhang Na Li Xiaocheng Fan Ying Li Influence of verapamil on the pharmacokinetics of oridonin in rats
description	Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still unclear. Objective: This study investigated the effect of verapamil on the pharmacokinetics of oridonin in rats and clarified its main mechanism. Materials and methods: The pharmacokinetic profiles of oral administration of oridonin (20 mg/kg) in Sprague-Dawley rats with two groups of six animals each, with or without pre-treatment of verapamil (10 mg/kg/day for 7 days) were investigated. The effects of verapamil on the transport and metabolic stability of oridonin were also investigated using Caco-2 cell transwell model and rat liver microsomes. Results: The results showed that verapamil could significantly increase the peak plasma concentration (from 146.9 ± 10.17 to 193.97 ± 10.53 ng/mL), and decrease the oral clearance (from 14.69 ± 4.42 to 8.09 ± 3.03 L/h/kg) of oridonin. The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of oridonin from 1.67 to 1.15, and the intrinsic clearance rate of oridonin was decreased by the pre-treatment with verapamil (40.06 ± 2.5 vs. 36.09 ± 3.7 µL/min/mg protein). Discussion and conclusions: These results indicated that verapamil could significantly change the pharmacokinetic profile of oridonin in rats, and it might exert these effects through increasing the absorption of oridonin by inhibiting the activity of P-gp, or through inhibiting the metabolism of oridonin in rat liver. In addition, the potential drug–drug interaction should be given special attention when verapamil is used with oridonin. Also, the dose of oridonin should be carefully selected in the clinic.
format	article
author	Jing Liu Ning Zhang Na Li Xiaocheng Fan Ying Li
author_facet	Jing Liu Ning Zhang Na Li Xiaocheng Fan Ying Li
author_sort	Jing Liu
title	Influence of verapamil on the pharmacokinetics of oridonin in rats
title_short	Influence of verapamil on the pharmacokinetics of oridonin in rats
title_full	Influence of verapamil on the pharmacokinetics of oridonin in rats
title_fullStr	Influence of verapamil on the pharmacokinetics of oridonin in rats
title_full_unstemmed	Influence of verapamil on the pharmacokinetics of oridonin in rats
title_sort	influence of verapamil on the pharmacokinetics of oridonin in rats
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/4e27aaa791904179aeb0edeac67b4784
work_keys_str_mv	AT jingliu influenceofverapamilonthepharmacokineticsoforidonininrats AT ningzhang influenceofverapamilonthepharmacokineticsoforidonininrats AT nali influenceofverapamilonthepharmacokineticsoforidonininrats AT xiaochengfan influenceofverapamilonthepharmacokineticsoforidonininrats AT yingli influenceofverapamilonthepharmacokineticsoforidonininrats
_version_	1718425479424245760

Influence of verapamil on the pharmacokinetics of oridonin in rats

Ejemplares similares