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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...

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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
Descripción
Sumario: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.