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

Summary

This study will examine the interaction of the HIV combination medication lopinavir/ritonavir with the herbal products echinacea, ginseng, and ginkgo biloba. Patients with HIV infection often take herbal products and dietary supplements in addition to their doctor-prescribed medicines to treat the disease, lessen the side effects of anti-viral drugs, and improve their overall well being. Alternative medicines such as these may, however, interfere with the elimination of lopinavir/ritonavir from the body, causing either higher or lower blood levels of these drugs than would be expected. This study will assess in healthy subjects any potential harms of taking echinacea, ginseng, or ginkgo biloba together with lopinavir/ritonavir. Healthy normal volunteers between 18 and 50 years of age may be eligible for this study. Candidates are screened with a history, physical examination, and blood tests, including an HIV test and a pregnancy test for women. Pregnant women are excluded from the study. Participants come to the NIH Clinical Center after fasting overnight for the following procedures: Visits 1 and 2: A catheter (plastic tube) is placed in an arm vein to collect blood samples. After the first sample is drawn, the subject takes 8 mg of midazolam syrup and two fexofenadine tablets. Midazolam is a sedative, and fexofenadine (Allegra) is a medicine used to treat allergies. Subjects are given breakfast an hour after taking the drugs. Blood samples are collected at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 24 hours after taking the drugs to measure blood levels of fexofenadine. An extra sample is collected at the 4-hour mark to measure the midazolam level. The catheter is removed after the 8-hour blood draw and subjects are dismissed home. They return the following morning (visit 2) for the 24-hour blood draw. Visit 3: From 7 to 28 days after visit 1, subjects begin taking lopinavir/ritonavir capsules twice a day by mouth for a total of 29.5 days. On day 15 they return to the clinic for lopinavir/ritonavir blood levels as were done for fexofenadine, except that samples are collected once before breakfast and then at 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after the lopinavir/ritonavir dose. An extra sample is collected for routine tests. The catheter is removed after the 12-hour draw and the subject is dismissed home. The next morning, subjects begin taking one of the following: echinacea 500 mg 3 times a day; ginkgo biloba 120 mg twice a day; or ginseng 500 mg 3 times a day for 28 days. Visit 4: On the last day of taking lopinavir/ritonavir, subjects return to the clinic again for blood level measurements of these drugs as on visit 3, except that the catheter is removed and the subject dismissed home after the 8-hour blood draw. Visits 5 and 6: On the last day of taking the herbal supplement, subjects return to the clinic for repeat measurement of fexofenadine and midazolam levels, as described in visits 1 and 2. At the final visit (visit 6) an additional blood sample is collected for repeat laboratory testing. ...

Timeline

Start

2005-01

Primary completion

2011-01

Completion

2011-06

Publications

• Background Fairfield KM, Eisenberg DM, Davis RB, Libman H, Phillips RS. Patterns of use, expenditures, and perceived efficacy of complementary and alternative therapies in HIV-infected patients. Arch Intern Med. 1998 Nov 9;158(20):2257-64. doi: 10.1001/archinte.158.20.2257.
• Background Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, Kessler RC. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA. 1998 Nov 11;280(18):1569-75. doi: 10.1001/jama.280.18.1569.
• Background Risa KJ, Nepon L, Justis JC, Panwalker A, Berman SM, Cinti S, Wagener MM, Singh N. Alternative therapy use in HIV-infected patients receiving highly active antiretroviral therapy. Int J STD AIDS. 2002 Oct;13(10):706-13. doi: 10.1258/095646202760326471.

Drugs

Indications

No indication recorded.