Standardized Ginkgo biloba leaf extract (GBE) is a widely used dietary supplement for the treatment or prevention of Alzheimer's disease, failing memory, age-related dementias, etc. in Japan as well as the United State, and now a phytomedicine in many countries in Europe.1) GBE consists of many flavonoid glycosides and various unique diterpenes such as ginkgolides, which are potent inhibitors of platelet activating factor.1) It is highly likely that GBE is used in combination with various medicines by many patients.Previously, we reported that the simultaneous addition of GBE to the rat small intestine and liver microsomes inhibited the formation of N-demethyl diltiazem (MA), an active metabolite of diltiazem (DTZ) produced by a well-known drug metabolizing enzyme P450 (CYP) 3A, in a concentration-dependent manner.2) This inhibition appeared to be caused, at least in part, by a mechanism-based inhibition. Both the rate of formation of MA and total amount of CYP in intestinal or hepatic microsomes after a single oral pretreatment with GBE (20 mg/kg) decreased transiently. Furthermore, it was found the concomitant use of GBE in rats significantly increased the bioavailability after oral administration of DTZ, a typical substrate of CYP3A, as well as a highly extracted drug, while the elimination after intravenous administration of DTZ was slightly delayed by simultaneous oral treatment with GBE.2) These findings suggest that there is a possibility of potential pharmacokinetic interactions between GBE and other drugs that are both substrates for CYP3A and extensively extracted drugs.3,4) However, there are still many unclear points regarding the inhibitory mechanism of action because DTZ is a substrate of not only CYP3A, but also esterase in rats and humans, 5) and of the multidrug transporter P-glycoprotein (P-gp) which is expressed in normal tissues with excretory function, playing an important role in drug pharmacokinetics. [6][7][8] Therefore, in this study, we examined the effects of simultaneous oral treatment with GBE on the pharmacokinetics of nifedipine (NFP), which is a representative substrate of CYP3A, but not P-gp, [6][7][8] and is at first metabolized only to dehydronifedipine (NFPO) in the intestine and liver in both rats and humans, 9-13) after intravenous and oral administration of NFP to rats. MATERIALS AND METHODSChemicals GBE (Ginkgolon-24; Lot No. 830301034) powders were kindly provided by Tokiwa Phytochemical Co., Ltd. (Chiba, Japan). GBE was produced using a standard method by extraction from milled leaves with ethanol. The final quality of this extract was assured by maintaining the prescribed range of index components (over 24% flavonoid glycosides and 6% terpene lactones and less than 1 ppm ginkgolic acids). NFP, nicardipine (an internal standard for HPLC analysis) and polyethylene glycol (PEG) 400 were purchased from Wako Pure Chemical Ind., Ltd. (Osaka, Japan). All other chemicals were reagent-or HPLC-grade commercial products.Animals Nine-week-old male Wistar rats (Japan SLC, Inc., Hama...

The effects of turmeric extracts on the pharmacokinetics of nifedipine were examined in 10 healthy volunteers. An open-label and randomized crossover study was performed at 2-week intervals. In the control experiment, after a 10 h overnight fast, 10 mg of nifedipine (Adalat® capsule) was administered orally and blood was collected at 0, 0.5, 1, 2, 3, 4, 5, 6, and 8 h. In the combination experiment, the volunteers were orally administered 10 mg of nifedipine together with six tablets containing concentrated turmeric extract (480 mg of curcuminoid per six tablets), which is the general daily dose, and blood was sampled as above. The time profile of the plasma concentration of nifedipine in the control was comparable to that in combination with turmeric extract, as were the pharmacokinetic parameters: that is, the mean ratio of turmeric extract/control group (90% confidence interval: CI); C(max), 0.98 (0.95, 1.01) and AUC(0 - ∞) 1.00 (0.98, 1.02). In addition, the volunteers all completed the study without any serious adverse events. Consumption of the turmeric extract did not affect the pharmacokinetics of nifedipine after a single oral administration.