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 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 AUC0-12, 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.
Lab of Clinical Pharmacokinetics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Furong
F
Qiu
Jian
J
Jiang
Yueming
Y
Ma
Guangji
G
Wang
Chenglu
C
Gao
Xinfeng
X
Zhang
Liang
L
Zhang
Songcan
S
Liu
Min
M
He
Leilei
L
Zhu
Yujie
Y
Ye
Qiuye
Q
Li
Ping
P
Miao