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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。除了化疗外，同时进行高效抗逆转录病毒疗法(HAART)对于成功治疗与艾滋病相关的恶性肿瘤至关重要，如卡波西氏肉瘤(KS)和淋巴瘤(Bashoff，2000和Hengge，2002)。HAART的治疗不仅对已知的引发KS的艾滋病毒有直接作用，而且似乎对KS相关的疱疹病毒有抗病毒作用(Bashoff，2000和Hengge，2002)。然而，HAART具有很大的药物相互作用潜力，在某些情况下可能会影响其有效性，并危及艾滋病相关恶性肿瘤的治疗。HIV蛋白酶抑制剂由肝脏细胞色素P450 3A4(CYP3A4)酶代谢，这是许多常用药物和一些补充和替代医学(CAM)药物共有的代谢途径，使这类抗逆转录病毒药物对药物相互作用高度敏感(Flexner，2000)。例如，圣约翰麦芽汁和大蒜分别降低了HIV蛋白酶抑制剂依地那韦和沙奎那韦的浓度(Piscitelli，2000)。将吲哚那韦和沙奎那韦的浓度降低30%或更多会增加治疗失败的风险(Flexner，2000)。由于CAM在HIV和AIDS患者中非常流行，艾滋病相关恶性肿瘤患者可能正在使用其中一些药物，因此识别可能干扰HIV蛋白酶抑制物代谢的有害药物-草药相互作用非常重要，从而影响艾滋病相关恶性肿瘤的治疗。HIV蛋白水解酶抑制剂与多种代谢紊乱有关，包括周围性消瘦、中心性肥胖、血脂异常和血糖异常。这些异常的中心特征是胰岛素抵抗，这可能会增加心血管疾病和糖尿病的风险。西洋参(西洋参)被发现可以改善患有和不患有II型糖尿病的受试者的葡萄糖耐量(Vuksan，2000)。最近，HIV蛋白水解酶抑制剂吲哚那韦(Crixivan)被证明在健康志愿者中诱导葡萄糖耐量增加(Noor，2002)。因此，西洋参可能对应对糖耐量异常的HIV/AIDS患者有潜在的治疗益处。然而，西洋参是否会干扰依地那韦的新陈代谢尚不清楚。我们建议的目标是研究西洋参-吲哚那韦的药代动力学药物相互作用，并评价西洋参对吲哚那韦诱导的胰岛素抵抗的治疗作用。

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.