Drug Interactions of Echinacea, Ginseng, and Ginkgo Biloba Taken With Lopinavir/Ritonavir in Healthy Volunteers

• INCLUSION CRITERIA:

  1. Males and females between the ages of 18 and 50 years.
  2. Healthy by medical history and physical exam.
  3. Laboratory values within established guidelines for participation in clinical studies: AST less than or equal to 2 times the ULN; SCr less than or equal to ULN; hemoglobin equal to or greater than 11 g/dL (for both males and females).
  4. Ability to abstain from ingesting fruit juice during pharmacokinetic sampling periods (a total of 2 study days), and abstain from eating grapefruit or drinking grapefruit juice during the entire study period.
  5. Negative serum or urine pregnancy test for females of child-bearing potential.
  6. Females of child-bearing potential who are able and willing to practice abstinence or use non-hormonal effective methods of birth control during the study, such as condoms or diaphragms.

EXCLUSION CRITERIA:

1. Concomitant routine therapy with any prescription, over-the-counter, herbal, or holistic medications, including oral contraceptives, for 30 days prior to study participation. Intermittent use of any medication within 30 days prior to screening will be considered case by case by the principal investigator and the medically accountable investigator.

   • Concomitant therapy (chronic or intermittent) with any prescription, over-the-counter, or herbal drugs (including tinctures, foods, beverages, and gum) will not be allowed during the study duration, including any intermittent use of allergy medication.
   • Intermittent use of acetaminophen, non-steroidal anti-inflammatory medications (i.e. ibuprofen), and loperamide will be allowed during the study, but should not be taken on the days of pharmacokinetic blood sampling.
   • A daily multivitamin with minerals will be allowed during the study.
2. Inability to obtain venous access for blood sample collection.
3. The presence or history of any of the following: diabetes mellitus (clinical diagnosis based on current guidelines, HIV infection, active tuberculosis, cardiac disease (eg. Hypertension [SBP greater than 140 mmHG or DBP greater than 90 mmHG], heart failure, arrhythmia, etc.), renal disease, hepatitis or hepatic impairment, pancreatitis, bleeding disorders, internal bleeding (such as gastrointestinal or intracranial), respiratory disease (eg. asthma requiring maintenance pharmacologic therapy, chronic obstructive pulmonary disease, etc.), peptic ulcer disease, osteoporosis, osteonecrosis, atopy or atopic dermatitis, hormone sensitive cancers or conditions, organ transplant, seizure disorders, schizophrenia or other psychiatric illnesses that may interfere with the subject's ability to participate in the study, or any other condition that may interfere with the interpretation of the study results or not be in the best interest of the subject in the opinion of the investigators.
4. Plans for elective surgery during the investigation or within 1 month following completion for subjects in the gingko biloba arm of the study.
5. Positive serum or urine pregnancy test or breastfeeding female.
6. The presence of persistent diarrhea or malabsorption that would interfere with the subject's ability to absorb drugs.
7. Drug or alcohol abuse that may impair safety or adherence (more than 3 alcoholic drinks per day, on a daily basis).
8. History of intolerance or allergic reaction to any products containing echinacea, ginkgo biloba extract, or ginseng (including pills, tinctures, foods, beverages, and gum).
9. History of intolerance or allergic reaction to lopinavir, ritonavir, midazolam, or fexofenadine.
10. History of atopy including atopic dermatitis, bronchial asthma, multiple food allergies, or severe recurring allergic rhinitis.
11. Fasting total cholesterol greater than 240 mg/dL or fasting triglycerides greater than 400 mg/dL.
12. Use of nicotine-containing tobacco products, including cigarettes and chewing tobacco.