Bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir are members of the latest class of antiretrovirals available to treat human immunodeficiency virus (HIV) infection, the integrase strand transfer inhibitors. Integrase strand transfer inhibitors are potent inhibitors of the HIV integrase enzyme with IC90/95 values in the low nanogram per milliliter range and they retain antiviral activity against strains of HIV with acquired resistance to other classes of antiretrovirals. Each of the integrase strand transfer inhibitors have unique pharmacokinetic/pharmacodynamic properties, influencing their role in clinical use in specific subsets of patients. Cabotegravir, approved for use in Canada but not yet by the US Food and Drug Administration, is formulated in both oral and intramuscular formulations; the latter of which has shown efficacy as a long-acting extended-release formulation. Cabotegravir, raltegravir, and dolutegravir have minimal drug-drug interaction profiles, as their metabolism has minimal cytochrome P450 involvement. Conversely, elvitegravir metabolism occurs primarily via cytochrome P450 3A4 and requires pharmacokinetic boosting to achieve systemic exposures amenable to once-daily dosing. Bictegravir metabolism has similar contributions from both cytochrome P450 3A4 and uridine 5'-diphospho-glucuronosyltransferase 1A1. Bictegravir, dolutegravir, and raltegravir are recommended components of initial regimens for most people with HIV in the US adult and adolescent HIV treatment guidelines. This review summarizes and compares the pharmacokinetics and pharmacodynamics of the integrase strand transfer inhibitor agents, and describes specific pharmacokinetic considerations for persons with hepatic impairment, renal dysfunction, pregnancy, and co-infections.

译文

Bictegravir,cabotegravir,dolutegravir,elvitegravir和raltegravir是可用于治疗人类免疫缺陷病毒 (HIV) 感染 (整合酶链转移抑制剂) 的最新一类抗逆转录病毒药物的成员。整合酶链转移抑制剂是HIV整合酶的有效抑制剂,其IC90/95值在每毫升低纳克范围内,并且它们保留了对HIV菌株的抗病毒活性,对其他类型的抗逆转录病毒药物具有获得性抗性。每种整合酶链转移抑制剂具有独特的药代动力学/药效学特性,影响其在特定患者亚群中的临床应用作用。Cabotegravir已在加拿大批准使用,但尚未获得美国食品和药物管理局的批准,它以口服和肌内制剂配制; 后者已显示出长效缓释制剂的功效。Cabotegravir,raltegravir和dolutegravir具有最小的药物-药物相互作用,因为它们的代谢具有最小的细胞色素P450参与。相反,elviteggravir代谢主要通过细胞色素P450 3A4发生,并且需要药代动力学增强以实现适合每日一次给药的全身暴露。Bictegravir代谢对细胞色素P450 3A4和尿苷5 '-二磷酸葡萄糖醛酸基转移酶1A1的贡献相似。在美国成人和青少年HIV治疗指南中,大多数HIV患者推荐使用Bictegravir,dolutegravir和raltegravir。这篇综述总结并比较了整合酶链转移抑制剂的药代动力学和药效学,并描述了肝功能不全,肾功能不全,妊娠和合并感染患者的特定药代动力学考虑。

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