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Are adverse events of nevirapine and efavirenz related to plasma concentrations?奈韦拉平和依非韦伦的不良事件与血浆浓度有关吗?
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Lopinavir plasma levels in salvage regimes by a population of highly active antiretroviral therapy-treated HIV-1-positive patients.
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Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy.在一个开始接受三联抗逆转录病毒疗法的大型未接受过抗逆转录病毒治疗队列中,HIV耐药性突变的预测因素。
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Incidence and risk factors for nevirapine-associated rash.奈韦拉平相关皮疹的发病率及危险因素。
Eur J Clin Pharmacol. 2003 Sep;59(5-6):457-62. doi: 10.1007/s00228-003-0613-3. Epub 2003 Aug 12.
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Therapeutic drug monitoring of nelfinavir and indinavir in treatment-naive HIV-1-infected individuals.初治HIV-1感染个体中奈非那韦和茚地那韦的治疗药物监测
AIDS. 2003 May 23;17(8):1157-65. doi: 10.1097/00002030-200305230-00007.
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Subtherapeutic antiretroviral plasma concentrations in routine clinical outpatient HIV care.
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Evaluation of antiretroviral drug measurements by an interlaboratory quality control program.通过实验室间质量控制程序对抗逆转录病毒药物测量进行评估。
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Treatment failure of nelfinavir-containing triple therapy can largely be explained by low nelfinavir plasma concentrations.含奈非那韦的三联疗法治疗失败很大程度上可归因于奈非那韦血浆浓度较低。
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Human immunodeficiency virus type 1 genotypic and pharmacokinetic determinants of the virological response to lopinavir-ritonavir-containing therapy in protease inhibitor-experienced patients.在有蛋白酶抑制剂治疗经验的患者中,1型人类免疫缺陷病毒的基因型和药代动力学决定因素对含洛匹那韦-利托那韦治疗的病毒学反应。
Antimicrob Agents Chemother. 2002 Sep;46(9):2926-32. doi: 10.1128/AAC.46.9.2926-2932.2002.
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Therapeutic drug monitoring in HIV infection: current status and future directions.HIV感染中的治疗药物监测:现状与未来方向。
AIDS. 2002 Mar;16 Suppl 1:S5-37. doi: 10.1097/00002030-200203001-00002.

常规临床实践中,HIV感染成人非核苷类逆转录酶抑制剂和蛋白酶抑制剂浓度的变异性。

Variability in non-nucleoside reverse transcriptase and protease inhibitor concentrations among HIV-infected adults in routine clinical practice.

作者信息

Moltó José, Blanco Asunción, Miranda Cristina, Miranda José, Puig Jordi, Valle Marta, DelaVarga Meritxell, Fumaz Carmina R, Barbanoj Manuel José, Clotet Bonaventura

机构信息

Lluita Contra la SIDA Foundation, Badalona, Barcelona, Spain.

出版信息

Br J Clin Pharmacol. 2006 Nov;62(5):560-6. doi: 10.1111/j.1365-2125.2006.02694.x.

DOI:10.1111/j.1365-2125.2006.02694.x
PMID:17061963
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1885171/
Abstract

AIMS

The objective of this study was to assess interindividual variability in trough concentrations of plasma of non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) among HIV-infected adults in a routine outpatient setting.

METHODS

One hundred and seventeen patients who attended our clinic for routine blood tests, and who were receiving antiretroviral therapy which included NNRTI or PI were studied. Patients were not informed that drug concentrations were going to be measured until blood sampling. The times of the last antiretroviral dose and of blood sampling were recorded. Drug concentrations were considered optimal if they were above the proposed minimum effective value. In addition, efavirenz, nevirapine and atazanavir concentrations were considered potentially toxic if they were > 4.0 mg l(-1), > 6.0 mg l(-1) and > 0.85 mg l(-1), respectively.

RESULTS

Overall, interindividual variability of NNRTI and PI concentrations in plasma was approximately 50%, and only 68.4% of the patients had drug concentrations within the proposed therapeutic range. Poor adherence explained only 35% of subtherapeutic drug concentrations.

CONCLUSION

Interindividual variability in trough concentrations of NNRTI and PI among HIV-infected adults is large in routine clinical practice, with drug concentrations being outside the therapeutic window in a significant proportion of patients. These findings provide further evidence that therapeutic drug monitoring may be useful to guide antiretroviral therapy in clinical practice.

摘要

目的

本研究的目的是评估在常规门诊环境中,感染人类免疫缺陷病毒(HIV)的成年人中非核苷类逆转录酶抑制剂(NNRTI)和蛋白酶抑制剂(PI)血浆谷浓度的个体间差异。

方法

对117名到我们诊所进行常规血液检查、正在接受包含NNRTI或PI的抗逆转录病毒治疗的患者进行了研究。在采血之前,患者未被告知将要测量药物浓度。记录最后一次抗逆转录病毒药物剂量的时间和采血时间。如果药物浓度高于建议的最低有效值,则认为是最佳的。此外,如果依非韦伦、奈韦拉平和阿扎那韦的浓度分别>4.0mg/L、>6.0mg/L和>0.85mg/L,则认为具有潜在毒性。

结果

总体而言,血浆中NNRTI和PI浓度的个体间差异约为50%,只有68.4%的患者药物浓度在建议的治疗范围内。依从性差仅解释了35%的低于治疗浓度的药物情况。

结论

在常规临床实践中,感染HIV的成年人中NNRTI和PI谷浓度的个体间差异很大,相当一部分患者的药物浓度超出治疗窗。这些发现进一步证明,治疗药物监测可能有助于在临床实践中指导抗逆转录病毒治疗。