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

Abstract EN

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 Cmax of midazolam to increase by 87% compared with control.

After 10 days of the danshen extract intake, the mean AUC0–12, Cmax, and t1/2 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.