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

Table 1

Pharmacokinetic parameters of midazolam and 1-hydroxymidazolam after the administration of a single dose of 15 mg of midazolam in 12 healthy volunteers before and after single- and multiple-dose coadministration of the ethanol extract of danshen.

PK Parameter	Control	Single dose	P value*	Multiple dose	P value*
Midazolam
𝐶max (ng/mL)	95.17±39.01	163.57±86.36	0.00	39.55±18.52	0.00
𝑇max (h)	0.69±0.60	0.35±0.13	0.07	0.79±0.65	0.68
AUC0--12 (ng·h/mL)	219.86±64.67	213.85±86.31	0.70	42.24±15.74	0.00
AUC0--∞ (ng·h/mL)	221.76±63.78	218.15±83.22	0.65	44.55±17.68	0.00
𝑡1/2 (h)	4.20±0.76	4.01±1.08	0.61	2.20±0.90	0.00
CL/F (L/h)	67.64±20.05	75.78±27.94	0.18	393.71±157.14	0.00
1-Hydroxymidazolam
𝐶max (ng/mL)	26.78±11.00	45.04±15.09	0.01	20.48±13.70	0.18
𝑇max (h)	0.57±0.20	0.61±0.39	0.12	0.46±0.13	0.74
AUC0--12(ng·h/mL)	56.21±22.75	66.62±25.24	0.12	30.88±15.09	0.00
𝑡1/2 (h)	3.30±0.62	3.29±0.78	0.16	1.72±0.70	0.00
AUC(1OHmdz)/AUC(mdz)	0.26±0.15	0.32±0.15	0.08	0.77±0.53	0.00

Data are presented as mean ± SD. *P values are given for the differences with respect to control. The data were analyzed using a one-way analysis of variance with post hoc Dunnett’s procedure.