Dhami H, Fritz C E, Gankin B, Pak S H, Yi W, Seya M-J, Raffa R B, Nagar S
Temple University School of Pharmacy, Philadelphia, PA, USA.
J Clin Pharm Ther. 2009 Apr;34(2):147-60. doi: 10.1111/j.1365-2710.2008.00978.x.
Since the recognition of human acquired immune deficiency syndrome, numerous classes of pharmacologic therapeutics have been developed to manage the disease. Current therapy includes co-administration of combinations of drugs classified by their mechanism of action as 'transcriptase inhibitors', 'protease inhibitors', 'integrase inhibitors' and the more recent 'fusion inhibitors'. This review focuses on the chemokine system and the recognition of chemokine receptors as targets for anti-human immunodeficiency virus (HIV) therapy. The FDA-approved chemokine (C-C motif) receptor 5 (CCR5) antagonist maraviroc (Selzentry) is discussed in detail, along with another compound vicriviroc, currently in clinical trials. The mechanism of action, pharmacokinetics, toxicity and current status of research on CCR5 antagonists is described. Further, potential therapeutic uses of these agents other than anti-HIV therapy are discussed.
自从认识到人类获得性免疫缺陷综合征以来,已经开发了许多类药物疗法来治疗该疾病。目前的治疗方法包括联合使用根据作用机制分类为“转录酶抑制剂”、“蛋白酶抑制剂”、“整合酶抑制剂”以及最近的“融合抑制剂”的药物组合。本综述聚焦于趋化因子系统以及将趋化因子受体识别为抗人类免疫缺陷病毒(HIV)治疗的靶点。详细讨论了美国食品药品监督管理局(FDA)批准的趋化因子(C-C基序)受体5(CCR5)拮抗剂马拉维若(Selzentry),以及另一种目前正在进行临床试验的化合物维克维若。描述了CCR5拮抗剂的作用机制、药代动力学、毒性和当前研究现状。此外,还讨论了这些药物除抗HIV治疗之外的潜在治疗用途。