Cargando…

Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers

The aim of this study was to investigate the effect of single- and multidose administration of the ethanol extract of danshen on in vivo CYP3A activity in healthy volunteers. A sequential, open-label, and three-period pharmacokinetic interaction study design was used based on 12 healthy male individ...

Descripción completa

Detalles Bibliográficos
Autores principales: Qiu, Furong, Jiang, Jian, Ma, Yueming, Wang, Guangji, Gao, Chenglu, Zhang, Xinfeng, Zhang, Liang, Liu, Songcan, He, Min, Zhu, Leilei, Ye, Yujie, Li, Qiuye, Miao, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816049/
https://www.ncbi.nlm.nih.gov/pubmed/24223062
http://dx.doi.org/10.1155/2013/730734
_version_ 1782289485736706048
author Qiu, Furong
Jiang, Jian
Ma, Yueming
Wang, Guangji
Gao, Chenglu
Zhang, Xinfeng
Zhang, Liang
Liu, Songcan
He, Min
Zhu, Leilei
Ye, Yujie
Li, Qiuye
Miao, Ping
author_facet Qiu, Furong
Jiang, Jian
Ma, Yueming
Wang, Guangji
Gao, Chenglu
Zhang, Xinfeng
Zhang, Liang
Liu, Songcan
He, Min
Zhu, Leilei
Ye, Yujie
Li, Qiuye
Miao, Ping
author_sort Qiu, Furong
collection PubMed
description The aim of this study was to investigate the effect of single- and multidose administration of the ethanol extract of danshen on in vivo CYP3A activity in healthy volunteers. A sequential, open-label, and three-period pharmacokinetic interaction study design was used based on 12 healthy male individuals. The plasma concentrations of midazolam and its metabolite 1-hydroxymidazolam were measured. Treatment with single dose of the extract caused the mean C (max) of midazolam to increase by 87% compared with control. After 10 days of the danshen extract intake, the mean AUC(0–12), C (max), and t (1/2) of midazolam were decreased by 79.9%, 66.6%, and 43.8%, respectively. The mean clearance of midazolam was increased by 501.6% compared with control. The in vitro study showed that dihydrotanshinone I in the extract could inhibit CYP3A, while tanshinone IIA and cryptotanshinone could induce CYP3A. In conclusion, a single-dose administration of the danshen extract can inhibit intestinal CYP3A, but multidose administration can induce intestinal and hepatic CYP3A.
format Online
Article
Text
id pubmed-3816049
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-38160492013-11-12 Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers Qiu, Furong Jiang, Jian Ma, Yueming Wang, Guangji Gao, Chenglu Zhang, Xinfeng Zhang, Liang Liu, Songcan He, Min Zhu, Leilei Ye, Yujie Li, Qiuye Miao, Ping Evid Based Complement Alternat Med Research Article The aim of this study was to investigate the effect of single- and multidose administration of the ethanol extract of danshen on in vivo CYP3A activity in healthy volunteers. A sequential, open-label, and three-period pharmacokinetic interaction study design was used based on 12 healthy male individuals. The plasma concentrations of midazolam and its metabolite 1-hydroxymidazolam were measured. Treatment with single dose of the extract caused the mean C (max) of midazolam to increase by 87% compared with control. After 10 days of the danshen extract intake, the mean AUC(0–12), C (max), and t (1/2) of midazolam were decreased by 79.9%, 66.6%, and 43.8%, respectively. The mean clearance of midazolam was increased by 501.6% compared with control. The in vitro study showed that dihydrotanshinone I in the extract could inhibit CYP3A, while tanshinone IIA and cryptotanshinone could induce CYP3A. In conclusion, a single-dose administration of the danshen extract can inhibit intestinal CYP3A, but multidose administration can induce intestinal and hepatic CYP3A. Hindawi Publishing Corporation 2013 2013-10-08 /pmc/articles/PMC3816049/ /pubmed/24223062 http://dx.doi.org/10.1155/2013/730734 Text en Copyright © 2013 Furong Qiu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Qiu, Furong
Jiang, Jian
Ma, Yueming
Wang, Guangji
Gao, Chenglu
Zhang, Xinfeng
Zhang, Liang
Liu, Songcan
He, Min
Zhu, Leilei
Ye, Yujie
Li, Qiuye
Miao, Ping
Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers
title Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers
title_full Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers
title_fullStr Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers
title_full_unstemmed Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers
title_short Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers
title_sort opposite effects of single-dose and multidose administration of the ethanol extract of danshen on cyp3a in healthy volunteers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816049/
https://www.ncbi.nlm.nih.gov/pubmed/24223062
http://dx.doi.org/10.1155/2013/730734
work_keys_str_mv AT qiufurong oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT jiangjian oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT mayueming oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT wangguangji oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT gaochenglu oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT zhangxinfeng oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT zhangliang oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT liusongcan oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT hemin oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT zhuleilei oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT yeyujie oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT liqiuye oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers
AT miaoping oppositeeffectsofsingledoseandmultidoseadministrationoftheethanolextractofdanshenoncyp3ainhealthyvolunteers