Department of Pharmacy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia.
Center for Medical and Pharmaceutical Investigations and Quality Control, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia.
Int J Mol Sci. 2024 Feb 13;25(4):2230. doi: 10.3390/ijms25042230.
Rosmarinic acid (RA) is a phenolic compound with antiviral properties, often encountered in dietary supplements and herbal drugs. Data on the pharmacokinetics of RA are lacking in cases of the chronic use of supplements containing this compound, and only limited data on the metabolism and distribution of RA are available. The aim of the study was to investigate the plasma levels of RA after 12 weeks of use and determine potential interactions of RA and selected antiretroviral drugs. Patients infected with human immunodeficiency virus took a supplement containing RA for 12 weeks, after which the RA concentrations in the plasma samples were analyzed. A detailed in silico analysis was conducted in order to elucidate the potential interactions between RA and the drugs efavirenz, darunavir and raltegravir. It was found that RA can be detected in patients' plasma samples, mainly in the form of sulphoglucuronide. The potential interactions are suggested on the level of liver metabolizing enzymes and efflux P-glycoprotein, with RA competing with antiretroviral drugs as a substrate in metabolism and distribution systems. The present study suggests that the simultaneous use of RA and antiretroviral therapy (containing efavirenz, darunavir or raltegravir) may affect the plasma levels of RA after prolonged supplementation.
迷迭香酸（RA）是一种具有抗病毒特性的酚类化合物，常存在于膳食补充剂和草药药物中。在慢性使用含有这种化合物的补充剂的情况下，关于 RA 的药代动力学的数据是缺乏的，而且关于 RA 的代谢和分布的有限数据是可用的。本研究的目的是调查在使用 12 周后 RA 在血浆中的水平，并确定 RA 和选定的抗逆转录病毒药物之间的潜在相互作用。感染人类免疫缺陷病毒的患者服用含有 RA 的补充剂 12 周，之后分析血浆样本中的 RA 浓度。为了阐明 RA 与药物依非韦伦、达芦那韦和拉替拉韦之间的潜在相互作用，进行了详细的计算机模拟分析。结果发现，RA 可以在患者的血浆样本中检测到，主要以硫酸葡萄糖醛酸酯的形式存在。潜在的相互作用是在肝代谢酶和外排 P-糖蛋白的水平上提出的，RA 作为代谢和分布系统中的底物与抗逆转录病毒药物竞争。本研究表明，RA 和抗逆转录病毒疗法（含有依非韦伦、达芦那韦或拉替拉韦）的同时使用可能会影响长期补充后 RA 的血浆水平。
