Effect of Ginkgo Biloba on Phenytoin Elimination
Effect of Ginkgo Biloba on Phenytoin Elimination
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
 needlestick.

 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
 principal investigator.

 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.