Effect of Ginkgo Biloba on Phenytoin Elimination

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00011063
First received: February 9, 2001
Last updated: March 3, 2008
Last verified: January 2001
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Ginkgo Biloba
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: Evaluation of the Effect of Ginkgo Biloba on Phenytoin Pharmacokinetics

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 12
Study Start Date: February 2001
Estimated Study Completion Date: April 2001
Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00011063

Locations
United States, Maryland
Warren G. Magnuson Clinical Center (CC)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00011063     History of Changes
Other Study ID Numbers: 010080, 01-CC-0080
Study First Received: February 9, 2001
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Anti-Epileptic
CYP2C9
Herbal
Interaction
Metabolism
Drug Interaction
Drug Metabolism
Ginko Biloba
Healthy Volunteer

Additional relevant MeSH terms:
Phenytoin
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 28, 2014