Studies on Interactions between Functional Foods or Dietary Supplements and Medicines. IV. Effects of Ginkgo biloba Leaf Extract on the Pharmacokinetics and Pharmacodynamics of Nifedipine in Healthy Volunteers

Yoshioka, Mutsunobu; Ohnishi, Noriaki; Koishi, Tomokazu; Obata, Yukihisa; Nakagawa, Masataka; Matsumoto, Tsuyoshi; Tagagi, Kentaro; Takara, Koji; Ohkuni, Tsuyoshi; Yokoyama, Teruyoshi; Kuroda, Kazuo

doi:10.1248/bpb.27.2006

Cited by 50 publications

(25 citation statements)

References 20 publications

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“…There is a report that the effects of Ginkgo extract (EGb 761) on drug metabolizing enzymes are specific to rats and may not be extrapolated to humans 14) ; however, according to more recent clinical reports, the interaction of GBE with anti-diabetic agents, anti-ulcer agents and antiplatelet/anti-coagulant agents has been demonstrated. [15][16][17][18] These reports support our postulation that long-term intake of GBE as a supplement in elderly people should be carefully monitored because of the likelihood of interaction with other drugs.…”

Section: Discussionsupporting

confidence: 66%

Long-Term Feeding of Ginkgo biloba Extract Impairs Peripheral Circulation and Hepatic Function in Aged Spontaneously Hypertensive Rats

Tada

Kagota

Kubota

et al. 2008

Biological & Pharmaceutical Bulletin

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Dietary supplements are often taken for a healthy lifestyle, and their number and type have greatly increased. Ginkgo biloba extract (GBE), which is the leaf extract of Ginkgo biloba, is one of the most used herbal dietary supplements in the world. GBE products are marketed as a dietary supplement in Japan. In some European countries, GBE, designated as EGb 761, is clinically used for cerebral insufficiency, such as intermittent claudication, dementia and equilibrium disorders. [1][2][3][4] According to a recent prospective community-based cohort study 5) and a randomized, placebo-controlled, doubleblind clinical trial, 6) treatment with Ginkgo biloba extract increases the probability of survival in the elderly population and efficacy in patients aged 50 years or above with Alzheimer's disease or vascular dementia.We have previously demonstrated that GBE has an inhibitory effect on rising blood pressure and the improvement of vasodilation in young spontaneously hypertensive rats (SHR) 7) ; however, little is known about the cardiovascular therapeutic action of GBE in older SHR. Furthermore, we have demonstrated that long-term GBE intake induces marked hepatic hypertrophy and the induction of hepatic metabolic enzymes in young rats, leading to an increased risk of interaction with various medicines. 8,9) A recent report indicated that care should be taken with the combination of GBE and anti-diabetic drugs in terms of the potential interactions, especially in elderly patients.10) Thus, to investigate the safety and utility of GBE in cardiovascular and hepatic functions in the elderly, in the present study we examined the effects of long-term GBE feeding on the cardiovascular system and hepatic metabolic enzyme expression in 50-week-old male SHR. MATERIALS AND METHODS Animals and DietsMale spontaneously hypertensive rats (SHR/Izm; SHR) were purchased from Japan SLC (Hamamatsu, Japan). Experiments were performed in accordance with the Guiding Principles for Care and Use of Laboratory Animals approved by The Japanese Pharmacological Society. A standardized powder form of GBE was kindly supplied by Tama Biochemical Co., Ltd. (Tokyo, Japan). GBE contained 24.2% flavonoids (12.4% quercetin) and 9.4% terpenes, and its composition was similar to that of EGb 761 used in European countries. At 50 weeks of age, the rats were divided into two groups by determination of body weight, blood pressure and heart rate, and then administrated a commercial rodent diet (CE-2; Clea Japan Inc., Tokyo Japan) (control group, nϭ5) or a GBE-containing diet (0.5% GBE addition to CE-2) (GBE group, nϭ6) for 4 weeks, respectively. We have already demonstrated that 4-week treatment with GBE has beneficial effects on cardiovascular function in young SHR 7) ; therefore, in the present study, the same conditions of dose and period used in young rats were used to investigate the effects of GBE in aged SHR. In general, the dosage of GBE is not limited by age when used as a supplement.Once a week during the experiment, in unanaesthetized rats, blood p...

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Section: Discussionsupporting

confidence: 66%

Long-Term Feeding of Ginkgo biloba Extract Impairs Peripheral Circulation and Hepatic Function in Aged Spontaneously Hypertensive Rats

Tada

Kagota

Kubota

et al. 2008

Biological & Pharmaceutical Bulletin

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“…Ginkgoaceae) are used for the treatment of cognitive impairments, dementia, intermittent claudication and tinnitus [2,3,4,5]. The effect of ginkgo on various CYP isoforms as well as on P-glycoprotein has been investigated in a number of clinical trials by using different probe drugs, such as alprazolam, midazolam, diazepam, nifedipine (CYP3A4), caffeine (CYP1A2), chlorzoxazone (CYP2E1), debrisoquine (CYP2D6), tolbutamide, diclofenac, flurbiprofen (CYP2C), omeprazole, voriconazole (CYP2C19), fexofenadine, digoxin and talinolol (P-glycoprotein substrates) [55,56,72,73,74,75,76,77,78,79,80,81,82]. Given the heterogeneity of the results, firm conclusions cannot be drawn.…”

Section: Clinical Interactions Between Herbs and Conventional Drugsmentioning

confidence: 99%

Interactions between Herbs and Conventional Drugs: Overview of the Clinical Data

2012

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This article provides an overview of the clinical evidence of interactions between herbal and conventional medicines. Herbs involved in drug interactions – or that have been evaluated in pharmacokinetic trials – are discussed in this review. While many of the interactions reported are of limited clinical significance and many herbal products (e.g. black cohosh, saw palmetto, echinacea, hawthorn and valerian) seem to expose patients to minor risk under conventional pharmacotherapy, a few herbs, notably St. John’s wort, may provoke adverse events sufficiently serious to endanger the patients’ health. Healthcare professionals should remain vigilant for potential interactions between herbal medicines and prescribed drugs, especially when drugs with a narrow therapeutic index are used.

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“…Supplementation led to a 17% decrease in the AUC of alprazolam, a probe drug for CYP3A4 (P < .05). 104 One final study conducted by Yoshioka et al 105 examined the effects of the administration of Ginkgo biloba leaf extract on the pharmacokinetics and pharmacodynamics of nifedipine and its metabolite; nifedipine is a CYP3A4 substrate. The extract was standardized to greater than 24% flavonoid glycosides, 6% terpene lactones, and less than 1 ppm Ginkgo bilobalic acids.…”

Section: Human and Clinical Studiesmentioning

confidence: 99%

Drug—Botanical Interactions: A Review of the Laboratory, Animal, and Human Data for 8 Common Botanicals

2009

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Many Americans use complementary and alternative medicine (CAM) to prevent or alleviate common illnesses, and these medicines are commonly used by individuals with cancer. These medicines or botanicals share the same metabolic and transport proteins, including cytochrome P450 enzymes (CYP), glucuronosyltransferases (UGTs), and P-glycoprotein (Pgp), with over-thecounter and prescription medicines increasing the likelihood of drug-botanical interactions. This review provides a brief description of the different proteins, such as CYPs, UGTs, and Pgp. The potential effects of drug-botanical interactions on the pharmacokinetics and pharmacodynamics of the drug or botanical and a summary of the more common models used to study drug metabolism are described. The remaining portion of this review summarizes the data extracted from several laboratory, animal, and clinical studies that describe the metabolism, transport, and potential interactions of 8 selected botanicals. The 8 botanicals include black cohosh, Echinacea, garlic, Gingko biloba, green tea, kava, milk thistle, and St John's wort; these botanicals are among some of the more common botanicals taken by individuals with cancer. These examples are included to demonstrate how to interpret the different studies and how to use these data to predict the likelihood of a clinically significant drug-botanical interaction.

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Studies on Interactions between Functional Foods or Dietary Supplements and Medicines. IV. Effects of Ginkgo biloba Leaf Extract on the Pharmacokinetics and Pharmacodynamics of Nifedipine in Healthy Volunteers

Cited by 50 publications

References 20 publications

Long-Term Feeding of Ginkgo biloba Extract Impairs Peripheral Circulation and Hepatic Function in Aged Spontaneously Hypertensive Rats

Long-Term Feeding of Ginkgo biloba Extract Impairs Peripheral Circulation and Hepatic Function in Aged Spontaneously Hypertensive Rats

Interactions between Herbs and Conventional Drugs: Overview of the Clinical Data

Drug—Botanical Interactions: A Review of the Laboratory, Animal, and Human Data for 8 Common Botanicals

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