Pharmacokinetic Parameters of HIV-1 Protease Inhibitors.,ChemMedChem

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Pharmacokinetic Parameters of HIV-1 Protease Inhibitors.
ChemMedChem ( IF 3.6 ) Pub Date : 2020-05-10 , DOI: 10.1002/cmdc.202000101
André L C S Nascimento ₁ , Richard P Fernandes ₂ , Christian Quijia ₃ , Victor H S Araujo ₃ , Juliana Pereira ₁ , Jerusa S Garcia ₁ , Marcello G Trevisan ₁ , Marlus Chorilli ₃

Affiliation

Since the beginning of the HIV epidemic, research has been carried out to control the virus. Understanding the mechanisms of replication has given access to the various classes of drugs that over time have transformed AIDS into a manageable chronic disease. The class of protease inhibitors (PIs) gained notice in anti‐retroviral therapy, once it was found that peptidomimetic molecules act by blocking the active catalytic center of the aspartic protease, which is directly related to HIV maturation. However, mutations in enzymatic internal residues are the biggest issue for these drugs, because a small change in biochemical interaction can generate resistance. Low plasma concentrations of PIs favor viral natural selection; high concentrations can inhibit even partially resistant enzymes. Food‐drug/drug‐drug interactions can decrease the bioavailability of PIs and are related to many side effects. Therefore, this review summarizes the pharmacokinetic properties of current PIs, the changes when pharmacological boosters are used and also lists the major mutations to help understanding of how long the continuous treatment can ensure a low viral load in patients.

中文翻译：

HIV-1蛋白酶抑制剂的药代动力学参数。

自从HIV流行开始以来，就进行了控制该病毒的研究。了解复制的机制使人们可以使用各种药物，这些药物随着时间的推移已将艾滋病转变为可控制的慢性病。一旦发现拟肽分子通过阻断天冬氨酸蛋白酶的活性催化中心而起作用，则该类蛋白酶抑制剂（PIs）在抗逆转录病毒疗法中引起了人们的关注，这与HIV的成熟直接相关。但是，酶促内部残基的突变是这些药物的最大问题，因为生化相互作用的微小变化会产生耐药性。PI的血浆浓度低有利于病毒的自然选择。高浓度甚至可以抑制部分抗性的酶。食品/药物之间的相互作用会降低PI的生物利用度，并且与许多副作用有关。因此，本综述总结了当前PI的药代动力学特性，使用药理增强剂时的变化，并列出了主要突变，以帮助了解持续治疗可以确保患者低病毒载量的时间。

更新日期：2020-06-23

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