Effect of danshen extract on the activity of CYP3A4 in healthy volunteers.
OBJECTIVE
To assess the effect of danshen extract on CYP3A4 activity using midazolam as an in vivo probe.


METHODS
A sequential, open-label, two-period pharmacokinetic interaction study design was used to compare midazolam pharmacokinetic parameters before and after 14 days of administration of danshen tablets. Twelve healthy volunteers received a single oral dose (15 mg) of midazolam followed by danshen tablets (four tablets orally, three times a day) for 14 days. On the last day of the study they received four danshen tablets with a 15 mg midazolam tablet and plasma concentrations of midazolam and its corresponding metabolite 1-hydroxylmidazolam were measured prior to and after the administration of danshen tablets periodically for 12 h.


RESULTS
The 90% confidence intervals of C(max,)t(1/2), CL/F and AUC(0,infinity) of midazolam before and after administration of danshen tablets were (0.559, 0.849), (0.908, 1.142), (1.086, 1.688) and (0.592, 0.921), respectively; and those of C(max), t(1/2) and AUC(0,infinity) of 1-hydroxylmidazolam after vs. before administration of danshen tablets were (0.633, 0.923), (0.801, 1.210) and (0.573, 0.980), respectively. Ratios of geometric LS means of C(max(1OHMid)) : C(max(Mid)) and AUC(max(1OHMid)) : AUC(max(Mid)) (after vs. before 14-day danshen) were 1.072 and 1.035, respectively.


CONCLUSIONS
Our findings suggest that multiple dose administration of danshen tablets may induce CYP3A4 in the gut. Accordingly, caution should be taken when danshen products are used in combination with therapeutic drugs metabolized by CYP3A.
Qiu
Furong
F
Laboratory of Clinical Pharmacokinetics, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Wang
Guangji
G
Zhang
Rong
R
Sun
Jianguo
J
Jiang
Jian
J
Ma
Yueming
Y
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002681:China; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics*; D027561:Salvia miltiorrhiza; D055815:Young Adult
D004365:Drugs, Chinese Herbal; D006993:Hypnotics and Sedatives; C028972:dan-shen root extract; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D008874:Midazolam