Effects of Ginkgo biloba extracts on diazepam metabolism: a pharmacokinetic study in healthy Chinese male subjects.
OBJECTIVE
It has been reported that Ginkgo biloba extract (GBE) is an inducer or inhibitor of microsomal cytochrome P450 (CYP) 2C19, and diazepam is a substrate of CYP2C19. Thus, it could be expected that GBE may alter the metabolism of diazepam.


METHODS
The pharmacokinetic parameters of diazepam and one of its metabolites, N-demethyldiazepam, were compared after oral administration of diazepam (10 mg) in the absence or presence of oral GBE (120 mg bid, for 28 days) in 12 healthy volunteers. The pharmacokinetic analysis was performed using a noncompartmental method.


RESULTS
The 90% confidence intervals (CIs) of the ratios of mean pharmacokinetic parameters of diazepam presence and absence of GBE were well within the 80-125% bioequivalence range, indicating no pharmacokinetic interaction. The ratio of AUC(0-408) with GBE to AUC(0-408) without GBE was 95.2 (90%CI: 91.6-98.8) and 101.8 (90%CI: 99.4-104.1) for diazepam and N-desmethyldiazepam, respectively. The two drugs were well tolerated, and no drug-related serious adverse events were reported.


CONCLUSIONS
The above data suggest that GBE, when taken in normally recommended doses over a 4-week time period, may not affect the pharmacokinetics of diazepam via CYP2C19 and the excretion of N-desmethyldiazepam in healthy volunteers. No drug-drug interaction was observed between GBE and diazepam.
Zuo
Xiao-Cong
XC
Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
Zhang
Bi-Kui
BK
Jia
Su-Jie
SJ
Liu
Shi-Kun
SK
Zhou
Ling-Yun
LY
Li
Jing
J
Zhang
Jie
J
Dai
Ling-Ling
LL
Chen
Ben-Mei
BM
Yang
Guo-Ping
GP
Yuan
Hong
H
D044466:Asian People; D003975:Diazepam / Q000493:pharmacokinetics*; D020441:Ginkgo biloba; D041743:Herb-Drug Interactions; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D008297:Male; D010936:Plant Extracts / Q000009:adverse effects*; D011794:Quercetin / Q000097:blood; D055815:Young Adult
D010936:Plant Extracts; C001380:6 beta-hydroxycortisol; D011794:Quercetin; D003975:Diazepam; D006854:Hydrocortisone