Gagliardi Anna, Bajraktari-Sylejmani Gzona, Barocelli Elisabetta, Weiss Johanna, Rigalli Juan Pablo
Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Department of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
Life (Basel). 2023 Aug 14;13(8):1745. doi: 10.3390/life13081745.
Drug-metabolizing enzymes (DMEs) and transporters play a major role in drug efficacy and safety. They are regulated at multiple levels and by multiple factors. Estimating their expression and activity could contribute to predicting drug pharmacokinetics and their regulation by drugs or pathophysiological situations. Determining the expression of these proteins in the liver, intestine, and kidney requires the collection of biopsy specimens. Instead, the isolation of extracellular vesicles (EVs), which are nanovesicles released by most cells and present in biological fluids, could deliver this information in a less invasive way. In this article, we review the use of EVs as surrogates for the expression and activity of DMEs, uptake, and efflux transporters. Preliminary evidence has been provided for a correlation between the expression of some enzymes and transporters in EVs and the tissue of origin. In some cases, data obtained in EVs reflect the induction of phase I-DMEs in the tissues. Further studies are required to elucidate to what extent the regulation of other DMEs and transporters in the tissues reflects in the EV cargo. If an association between tissues and their EVs is firmly established, EVs may represent a significant advancement toward precision therapy based on the biotransformation and excretion capacity of each individual.
药物代谢酶（DMEs）和转运体在药物疗效和安全性方面发挥着重要作用。它们受到多种水平和多种因素的调节。评估它们的表达和活性有助于预测药物的药代动力学以及药物或病理生理状况对其的调节作用。确定这些蛋白质在肝脏、肠道和肾脏中的表达需要采集活检标本。相反，细胞外囊泡（EVs）的分离可以以侵入性较小的方式提供这些信息，EVs是大多数细胞释放并存在于生物体液中的纳米囊泡。在本文中，我们综述了将EVs用作DMEs、摄取和外排转运体的表达和活性替代物的应用。已有初步证据表明，EVs中某些酶和转运体的表达与起源组织之间存在相关性。在某些情况下，从EVs中获得的数据反映了组织中I相药物代谢酶的诱导情况。需要进一步研究以阐明组织中其他DMEs和转运体的调节在多大程度上反映在EVs的货物中。如果组织与其EVs之间的关联能够牢固确立，那么基于个体的生物转化和排泄能力，EVs可能代表着精准治疗的重大进展。
