AMERICAN GINSENG (PANAX QUINQUEFOLIUS) IN INDIVAVIR-INDUCED INSULIN RESISTANCE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In addition to chemotherapy, concomitant treatment with highly active antiretroviral therapy (HAART) is essential for the successful treatment of AIDS-related malignancies such as Kaposi's sarcoma (KS) and lymphoma (Bashoff, 2000 and Hengge, 2002). Treatment with HAART not only has a direct action on HIV, known to trigger KS, but also seems to have an antiviral effect on the KS-associated herpes virus (Bashoff, 2000 and Hengge, 2002). However, HAART has a large potential for drug interactions that in some cases could affect its effectiveness and jeopardize the treatment of AIDS-related malignancies. HIV protease inhibitors, are metabolized by the hepatic cytochrome P450 3A4 (CYP3A4) enzyme, a metabolic pathway shared by many commonly used drugs and some complementary and alternative medicine (CAM) agents, making this class of antiretrovirals highly susceptible to drug interactions (Flexner, 2000). For instance, both St. John's wort and garlic, lowered concentrations of the HIV protease inhibitors indinavir and saquinavir, respectively (Piscitelli, 2000). Reducing concentrations of indinavir and saquinavir by 30% or more is associated with an increased risk of treatment failure (Flexner, 2000). Because CAM is very popular among patients with HIV and AIDS, and patients with AIDS-related malignancies could be using some of these agents, it is important to identify unwanted drug-herbal interactions that could interfere with the metabolism of HIV protease inhibitors and consequently compromise the treatment of AIDS-related malignancies. HIV protease inhibitors have been associated with multiple metabolic derangements including peripheral wasting, central adiposity, dyslipedemia, and glucose abnormalities. The central feature of these abnormalities is insulin resistance, which may increase the risk of cardiovascular disease and diabetes mellitus. American ginseng (Panax quinquefolius) was found to improve glucose tolerance in subjects with and without type II diabetes (Vuksan, 2000). Recently, the HIV protease inhibitor indinavir (Crixivan) was shown to induce glucose intolerance in healthy volunteers (Noor, 2002). Thus, American ginseng could be of potential therapeutic benefit for patients with HIV/AIDS coping with glucose intolerance. However, it is unknown whether American ginseng interferes with the metabolism of indinavir. The goal of our proposal is to study American ginseng-indinavir pharmacokinetic drug interaction and to evaluate American ginseng as a treatment for indinavir-induced insulin resistance.