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Pharmacokinetic Changes during Pregnancy According to Genetic Variants: a Prospective Study in HIV-Infected Patients Receiving Atazanavir-Ritonavir.根据遗传变异的妊娠期间药代动力学变化：接受阿扎那韦-利托那韦的 HIV 感染患者的前瞻性研究。
Antimicrob Agents Chemother. 2018 Jun 26;62(7). doi: 10.1128/AAC.00309-18. Print 2018 Jul.
2
PharmGKB summary: atazanavir pathway, pharmacokinetics/pharmacodynamics.药物基因组学知识库摘要：阿扎那韦途径，药代动力学/药效学。
Pharmacogenet Genomics. 2018 May;28(5):127-137. doi: 10.1097/FPC.0000000000000331.
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Atazanavir intracellular concentrations remain stable during pregnancy in HIV-infected patients.在感染 HIV 的患者中，阿扎那韦的细胞内浓度在怀孕期间保持稳定。
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Atazanavir exposure is effective during pregnancy regardless of tenofovir use.无论是否使用替诺福韦，孕期使用阿扎那韦均有效。
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Potential association between rosuvastatin use and high atazanavir trough concentrations in ritonavir-treated HIV-infected patients.瑞舒伐他汀的使用与利托那韦治疗的HIV感染患者中阿扎那韦高谷浓度之间的潜在关联。
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Tenofovir comedication does not impair the steady-state pharmacokinetics of ritonavir-boosted atazanavir in HIV-1-infected adults.在HIV-1感染的成人中，联用替诺福韦不会损害利托那韦增强的阿扎那韦的稳态药代动力学。
Eur J Clin Pharmacol. 2007 Oct;63(10):935-40. doi: 10.1007/s00228-007-0344-y. Epub 2007 Jul 31.
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Atazanavir plus low-dose ritonavir in pregnancy: pharmacokinetics and placental transfer.孕期使用阿扎那韦联合低剂量利托那韦：药代动力学与胎盘转运
AIDS. 2007 Nov 30;21(18):2409-15. doi: 10.1097/QAD.0b013e32825a69d1.
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A validated method for simultaneous quantification of four antiretrovirals in dried blood spot and plasma using LC-MS/MS: Application to efavirenz therapeutic drug monitoring in pregnant patients.一种采用 LC-MS/MS 同时定量测定干血斑和血浆中四种抗逆转录病毒药物的验证方法：在孕妇中应用依非韦伦治疗药物监测。
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Safety and exposure of once-daily ritonavir-boosted atazanavir in HIV-infected pregnant women.HIV 感染孕妇中每日一次利托那韦增强的阿扎那韦的安全性和暴露情况。
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Pharmacokinetics and Pharmacodynamics of Atazanavir in HIV-1-Infected Children Treated With Atazanavir Powder and Ritonavir: Combined Analysis of the PRINCE-1 and -2 Studies.在接受阿扎那韦粉剂和利托那韦治疗的 HIV-1 感染儿童中，阿扎那韦的药代动力学和药效学：PRINCE-1 和 -2 研究的综合分析。
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Antiretroviral Therapy in Pregnancy: A 2023 Review of the Literature.妊娠期抗逆转录病毒治疗：文献 2023 年回顾。
Curr HIV/AIDS Rep. 2024 Feb;21(1):1-10. doi: 10.1007/s11904-024-00688-y. Epub 2024 Jan 26.
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Dose of ritonavir-boosted atazanavir for HIV patient: a reappraisal based on genetic polymorphism epidemiology in Southeast Asia.用于HIV患者的利托那韦增强型阿扎那韦剂量：基于东南亚基因多态性流行病学的重新评估
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本文引用的文献

1
Atazanavir intracellular concentrations remain stable during pregnancy in HIV-infected patients.在感染 HIV 的患者中，阿扎那韦的细胞内浓度在怀孕期间保持稳定。
J Antimicrob Chemother. 2017 Nov 1;72(11):3163-3166. doi: 10.1093/jac/dkx274.
2
Pregnane X Receptor (PXR)-Mediated Gene Repression and Cross-Talk of PXR with Other Nuclear Receptors via Coactivator Interactions.孕烷X受体（PXR）介导的基因抑制以及PXR与其他核受体通过共激活因子相互作用的相互影响。
Front Pharmacol. 2016 Nov 25;7:456. doi: 10.3389/fphar.2016.00456. eCollection 2016.
3
Pregnancy-Induced Changes in Systemic Gene Expression among Healthy Women and Women with Rheumatoid Arthritis.健康女性和类风湿关节炎女性孕期全身基因表达的变化
PLoS One. 2015 Dec 18;10(12):e0145204. doi: 10.1371/journal.pone.0145204. eCollection 2015.
4
Intracellular accumulation of atazanavir/ritonavir according to plasma concentrations and OATP1B1, ABCB1 and PXR genetic polymorphisms.根据血浆浓度以及有机阴离子转运多肽1B1（OATP1B1）、ATP结合盒转运蛋白B1（ABCB1）和孕烷X受体（PXR）基因多态性分析阿扎那韦/利托那韦的细胞内蓄积情况。
J Antimicrob Chemother. 2014 Nov;69(11):3061-6. doi: 10.1093/jac/dku234. Epub 2014 Jul 4.
5
The dual role of pharmacogenetics in HIV treatment: mutations and polymorphisms regulating antiretroviral drug resistance and disposition.遗传药理学在 HIV 治疗中的双重作用：调控抗逆转录病毒药物耐药性和药物处置的突变和多态性。
Pharmacol Rev. 2012 Jul;64(3):803-33. doi: 10.1124/pr.111.005553.
6
Unboosted atazanavir for treatment of HIV infection: rationale and recommendations for use.未增强的阿扎那韦治疗 HIV 感染：原理和使用建议。
Drugs. 2012 Jun 18;72(9):1161-73. doi: 10.2165/11631070-000000000-00000.
7
Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and neonatal development in humanized UGT1 mice.妊娠相关 X 受体调控人源化 UGT1 小鼠妊娠和新生儿期肝脏葡萄糖醛酸化。
Hepatology. 2012 Aug;56(2):658-67. doi: 10.1002/hep.25671. Epub 2012 Jun 11.
8
Evaluation of the mean corpuscular volume of peripheral blood mononuclear cells of HIV patients by a coulter counter to determine intracellular drug concentrations.应用库尔特计数器评估 HIV 患者外周血单个核细胞的平均细胞体积以确定细胞内药物浓度。
Antimicrob Agents Chemother. 2011 Jun;55(6):2976-8. doi: 10.1128/AAC.01236-10. Epub 2011 Mar 14.
9
Population pharmacokinetic modeling of the association between 63396C->T pregnane X receptor polymorphism and unboosted atazanavir clearance.63396C->T 妊娠相关 X 受体多态性与未增强阿扎那韦清除率之间的群体药代动力学模型构建。
Antimicrob Agents Chemother. 2010 Dec;54(12):5242-50. doi: 10.1128/AAC.00781-10. Epub 2010 Oct 4.
10
The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir in HIV-infected men.SLCO1B1 多态性对 HIV 感染男性患者洛匹那韦和利托那韦血药浓度的影响。
Br J Clin Pharmacol. 2010 Jan;69(1):95-8. doi: 10.1111/j.1365-2125.2009.03551.x.

根据遗传变异的妊娠期间药代动力学变化：接受阿扎那韦-利托那韦的 HIV 感染患者的前瞻性研究。

Pharmacokinetic Changes during Pregnancy According to Genetic Variants: a Prospective Study in HIV-Infected Patients Receiving Atazanavir-Ritonavir.

机构信息

Unit of Infectious and Tropical Diseases, Department of Clinical and Experimental Sciences, University of Brescia and Spedali Civili General Hospital, Brescia, Italy

Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Turin, Italy.

出版信息

Antimicrob Agents Chemother. 2018 Jun 26;62(7). doi: 10.1128/AAC.00309-18. Print 2018 Jul.

DOI:10.1128/AAC.00309-18
PMID:29760129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6021630/
Abstract

Atazanavir-ritonavir concentrations change over time during pregnancy in HIV-positive patients; the impact of genetic variants is unknown. Twenty patients were enrolled in this study; plasma and intracellular concentrations of antiretrovirals were measured, in addition to single-nucleotide polymorphisms in transport-related genes. Linear logistic regression showed that genetic variants in organic-anion-transporter-1B1- and pregnane-X-receptor-encoding genes affected third-trimester atazanavir exposure. In this prospective study, genetic variants partially explained the observed interpatient variability in third-trimester exposure to antiretrovirals.

摘要

在感染 HIV 的孕妇中，阿扎那韦-利托那韦的浓度会随时间而变化；遗传变异的影响尚不清楚。本研究共纳入 20 例患者；除了转运相关基因的单核苷酸多态性外，还检测了抗逆转录病毒药物的血浆和细胞内浓度。线性逻辑回归显示，有机阴离子转运蛋白 1B1 和妊娠相关 X 受体编码基因的遗传变异影响了阿扎那韦在孕晚期的暴露。在这项前瞻性研究中，遗传变异部分解释了抗逆转录病毒药物在孕晚期观察到的个体间变异性。