Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Grahamstown, 6140, South Africa.
Biopharm Drug Dispos. 2011 Nov;32(8):458-70. doi: 10.1002/bdd.775.
The use of traditional/complementary/alternate medicines (TCAMs) in HIV/AIDS patients who reside in Southern Africa is quite common. Those who use TCAMs in addition to antiretroviral (ARV) treatment may be at risk of experiencing clinically significant pharmacokinetic (PK) interactions, particularly between the TCAMs and the protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Mechanisms of PK interactions include alterations to the normal functioning of drug efflux transporters, such as P-gp and/or CYP isoenzymes, such a CYP3A4 that mediate the absorption and elimination of drugs in the small intestine and liver. Specific mechanisms include inhibition and activation of these proteins and induction via the pregnane X receptor (PXR). Several clinical studies and case reports involving ARV-herb PK interactions have been reported. St John's Wort, Garlic and Cat's Claw exhibited potentially significant interactions, each with a PI or NNRTI. The potential for these herbs to induce PK interactions with drugs was first identified in reports of in vitro studies. Other in vitro studies have shown that several African traditional medicinal (ATM) plants and extracts may also demonstrate PK interactions with ARVs, through effects on CYP3A4, P-gp and PXR. The most complex effects were exhibited by Hypoxis hemerocallidea, Sutherlandia frutescens, Cyphostemma hildebrandtii, Acacia nilotica, Agauria salicifolia and Elaeodendron buchananii. Despite a high incidence of HIV/AIDs in the African region, only one clinical study, between efavirenz and Hypoxis hemerocallidea has been conducted. However, several issues/concerns still remain to be addressed and thus more studies on ATMs are warranted in order for more meaningful data to be generated and the true potential for such interactions to be determined.
在居住在南部非洲的 HIV/AIDS 患者中，使用传统/补充/替代药物（TCAMs）的情况相当普遍。那些在接受抗逆转录病毒（ARV）治疗的同时使用 TCAMs 的人可能面临临床显著的药代动力学（PK）相互作用的风险，特别是 TCAMs 与蛋白酶抑制剂（PIs）和非核苷类逆转录酶抑制剂（NNRTIs）之间。PK 相互作用的机制包括改变药物外排转运蛋白（如 P-糖蛋白和/或 CYP 同工酶）的正常功能，这些蛋白和同工酶如 CYP3A4 介导药物在小肠和肝脏中的吸收和消除。具体机制包括这些蛋白的抑制和激活以及通过孕烷 X 受体（PXR）的诱导。已经报道了涉及 ARV-草药 PK 相互作用的几项临床研究和病例报告。贯叶连翘、大蒜和猫爪草表现出潜在的显著相互作用，每种都与一种 PI 或 NNRTI 有关。这些草药与药物发生 PK 相互作用的潜力最初是在体外研究报告中确定的。其他体外研究表明，几种非洲传统药用（ATM）植物和提取物也可能通过对 CYP3A4、P-糖蛋白和 PXR 的影响，与 ARVs 发生 PK 相互作用。Hypoxis hemerocallidea、Sutherlandia frutescens、Cyphostemma hildebrandtii、Acacia nilotica、Agauria salicifolia 和 Elaeodendron buchananii 表现出最复杂的影响。尽管非洲地区 HIV/AIDS 的发病率很高，但仅进行了一项关于 efavirenz 和 Hypoxis hemerocallidea 之间的临床研究。然而，仍有一些问题/关注点需要解决，因此需要对 ATM 进行更多研究，以便生成更有意义的数据，并确定这种相互作用的真正潜力。
