This study will examine how the herbal remedy ginkgo biloba may affect the body's
elimination of other medicines. Many people take ginkgo biloba to improve memory, mental
alertness and overall feeling of well being. Since this product is considered a food
supplement and not a drug, it is not subject to the rigorous pre-market testing required for
prescription and over-the-counter (OTC) drugs. As a result, information has not been
collected on possible interactions between ginkgo biloba and other medications. This study
will look at how ginkgo biloba affects the elimination of phenytoin-a medication used to
treat patients with seizures.
Normal healthy volunteers 21 years of age or older may be eligible for this 40-day study.
Candidates will provide a medical history and undergo a physical examination and routine
blood tests. Women of childbearing age must use a reliable form of birth control other than
oral contraceptives ("the pill").
For at least 2 weeks before the study and throughout its duration, study participants may
not have any of the following: 1) medications that can affect platelet function (e.g.,
aspirin, Motrin, Advil, Nuprin, ibuprofen, etc.); 2) alcoholic beverages; 3) grapefruit and
grapefruit juice; and 4) all medications except those given by study personnel.
On day 1 of the study, subjects take one 500-mg dose of phenytoin at 8:00 A.M.. On an empty
stomach. (Subjects fast the night before taking the phenytoin and are allowed to eat
breakfast 2 hours after the dose). Blood samples are drawn just before dosing and again at
0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 32, 48, 72 and 96 hours after the dose. Blood drawn on
this first study day is collected through a catheter (small plastic tube) placed in a vein
to avoid multiple needlesticks. After the 12-hour sample is collected, the subject goes
home and then returns to the clinic for the remaining blood draws, which are taken by direct
When the blood sampling is completed, subjects begin ginkgo therapy. The NIH Clinical
Center provides participants a supply of 60-mg capsules of ginkgo to take twice a day (at 8
A.M. and 8 P.M..) for 4 weeks. At the end of the 4 weeks, subjects are given a second dose
of phenytoin as described above and repeat the blood sampling procedure. Subjects continue
taking ginkgo during this second phenytoin study.
Gingko biloba is a complementary or alternative medication used for purported cognitive
enhancing effects. Despite its widespread use there is limited data regarding potential for
drug interactions. The purpose of this study is to determine the effect of administration
of ginkgo for 4 weeks on single dose phenytoin pharmacokinetics. Eight healthy volunteers
will take a single 500mg dose of phenytoin capsules orally with serial blood samples
collected over 96 hours for determination of phenytoin pharmacokinetics. Following the
pharmacokinetic study subjects will begin taking 2, 60mg capsules (120mg total) of ginkgo
twice daily for 28 days. Following 28 days of ginkgo subjects will then again undergo
phenytoin pharmacokinetic evaluations with blood samples obtained over 96 hours for
determination of phenytoin pharmacokinetics. The ratio of geometric means for phenytoin
pharmacokinetic parameter values and 90% confidence intervals about the ratio of log
transformed parameter values will be calculated. Confidence intervals falling within the
80-125% range will characterize the pharmacokinetic parameter values before and after ginkgo
to be equivalent.
Male or female.
Healthy by medical history and physical exam.
Age greater than 21 years old.
No concurrent medications.
Non-smoker (for at least 6 months if prior history of smoking).
Laboratory values wihin the following guidelines: AST/SGOT less than or equal to 1.5
times the upper limit of normal; bilirubin less than or equal to the upper limit of
normal; serum creatinine less than or equal to the upper limit of normal; hemoglobin
greater than or equal to 10 g/dl; albumin NML.
Females of childbearing potential must be using a reliable form of birth control other
than hormonal contraceptives.
No concomitant therapy with other inhibitors or inducers of cytochrome P-450 mediated drug
metabolism within 30 days of study.
Must have the ability to remain free of chronic medications and alcohol for at least 2
weeks prior to and during the study.
No use of oral contraceptives (phenytoin, and potentially ginko, may induce the clearance
of oral contraceptive lead to potential oral contraceptive failure).
Must have the ability and willingness to avoid analgesics with antiplatelet activity for
at least 2 weeks prior to and during the study.
No presence of renal, hepatic, cardiovascular, hematologic, neurologic, psychiatric, or
respiratory disease or any other condition that may interfere with the interpretation of
the study results or not be in the best interests of the subject in the opinion of the
No positive serum pregnancy test.
No presence of persistent diarrhea or malabsorption that would interfere with the
patient's ability to adequately absorb drugs.
No drug or alcohol use that may impair safety or adherence.