天然生物增强剂:当前展望

S. Shanmugam
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引用次数: 4

摘要

全球各地的制药公司一直在为药物研发项目投入数十亿美元,迫切希望发现针对各种疾病的创新重磅药物。虽然确定具有治疗疾病的替代作用方式的新化学实体是制药公司的主要关切,但应用创新技术和技术以提高现有药物的生物利用度、功效和安全性也同样令人关切。事实上,提高治疗有效但生物利用度差的分子的生物利用度一直是药物开发计划的一个关键方面,因为它减少了药物剂量和频率,从而降低了患者的毒性和成本[1]。在导致药物生物利用度差的诸多因素中,药物本身的理化性质和生物屏障是两个主要因素[2]。药物的理化性质包括水溶性差、肠膜渗透性差、药物在胃肠道稳定性差等,生物屏障包括肝脏和肠道药物代谢酶(DMEs)和外排药物转运体(EDTs)。细胞色素P450 (CYP) DMEs在肠壁和肝脏中的药物代谢是这些DMEs底物药物生物利用度降低的主要原因[3]。除此之外,p -糖蛋白(P-gp)、乳腺癌耐药蛋白(BCRP)、多药耐药相关蛋白(MRP)等EDTs也会导致治疗活性药物,尤其是抗癌药物的生物利用度降低[3]。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Natural Bioenhancers: Current Outlook
Pharmaceutical companies around the globe have always been in the urge of discovering innovative blockbuster drugs for various ailments by spending billions of dollars for the drug discovery programmes. Although identification of new chemical entities (NCEs) with alternate mode of actions for diseases is a primary concern for the pharmaceutical companies, application of innovative techniques and technologies to increase the bioavailability, efficacy and safety of the already existing drugs are of no less concern as well. In fact, enhancing bioavailability of therapeutically potent but poorly bioavailable molecules has always been a crucial aspect of drug development programmes, as it reduces the drug dosage and frequency resulting in reduced toxicity and cost for the patients [1]. Among the various factors responsible for poor bioavailability of drugs, physiochemical properties of the drug itself and biological barriers are two predominant factors [2]. While physicochemical properties of the drug include poor aqueous solubility, poor intestinal membrane permeability, and poor stability of drug in gastrointestinal tract (GIT), biological barrier constitutes hepatic and intestinal drug metabolizing enzymes (DMEs) and efflux drug transporters (EDTs). The metabolism of drugs by cytochrome P450 (CYP) DMEs in the gut wall and in the liver is the major contributors of reduced bioavailability of drugs that are substrate to these DMEs [3]. In addition to this, EDTs such as P-glycoprotein (P-gp), breast cancer resistant protein (BCRP), multidrug resistant-associated protein (MRP) are also responsible for reduced bioavailability of the therapeutically active drugs, especially anticancer drugs [3].
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