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首页> 外文期刊>Current drug metabolism >Pharmacogenetic analysis of SNPs in genes involved in the pharmacokinetics and response to lopinavir/ritonavir therapy.
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Pharmacogenetic analysis of SNPs in genes involved in the pharmacokinetics and response to lopinavir/ritonavir therapy.

机译：涉及药物动力学和对洛匹那韦/利托那韦治疗的反应的基因中SNP的药物遗传学分析。

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摘要

Despite the known benefits and the experienced use of lopinavir/ritonavir (LPV/r) in the management of HIV infection, important interindividual variability in the pharmacokinetics (PKs) and the response to treatment with standard doses of this drug has been observed. Host genetic factors have been recently suggested as being responsible for part of this variability as they may affect the expression and functional activity of many proteins involved in the kinetic behavior, the immune recovery or the adverse effects related to LPV/r. Here, we present a genetic association study in 106 HIV-infected individuals collected over a period of 5 years with the aim of identifying and confirming single nucleotide polymorphisms (SNPs) with a significant influence on the PK parameters of LPV/r, the immunovirological response or toxicity derived from treatment with the studied drug. Genotyping was performed by MALDI-TOF and KASPar; LPV/r plasma concentrations were quantified using high-performance liquid chromatography with an ultraviolet detection system and the PK parameters were estimated using Bayesian algorithms. Genetic association analysis was performed with SPSS. The most significant associations were found between SNPs in the dopamine receptor D3 gene and the PK of LPV/r. Additionally, other suggestive relationships were established between genetic factors and the response during treatment with this drug. Thereby, identifying HIV-infected individuals who are at increased risk of achieve non-optimal LPV/r plasma concentrations with the emergence of toxicity, drug resistance or absence of clinical response could be helpful as a tool to optimize the LPV/r-based antiretroviral therapy.
机译：尽管已知洛匹那韦/利托那韦（LPV / r）具有已知的益处，并在治疗HIV感染方面有经验的使用，但已观察到药代动力学（PKs）的重要个体间差异以及标准剂量该药物对治疗的反应。最近已提出宿主遗传因素是造成这种变异的部分原因，因为它们可能影响许多参与动力学行为，免疫恢复或与LPV / r相关的不良反应的蛋白质的表达和功能活性。在这里，我们进行了一项针对5年内收集的106例HIV感染者的基因关联研究，目的是鉴定和确认对LPV / r PK参数，免疫病毒学应答有重大影响的单核苷酸多态性（SNP）。或研究药物治疗产生的毒性。基因分型由MALDI-TOF和KASPar进行;使用具有紫外检测系统的高效液相色谱法对LPV / r血浆浓度进行定量，并使用贝叶斯算法估算PK参数。用SPSS进行遗传关联分析。在多巴胺受体D3基因中的SNP与LPV / r的PK之间发现了最显着的关联。另外，在该药物治疗期间遗传因素与反应之间建立了其他暗示性关系。因此，鉴定出出现毒性，耐药性或缺乏临床反应的HIV感染者，其达到非最佳LPV / r血浆浓度的风险增加，可能有助于优化基于LPV / r的抗逆转录病毒药物治疗。

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