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1.
《HIV clinical trials》2013,14(1):41-47
Abstract

Purpose: The objective of this study was to examine lamivudine (3TC), zidovudine (ZDV), nelfinavir (NFV), and its active nelfinavir metabolite (M8) concentrations in paired maternal plasma and amniotic fluid samples to determine antiretroviral penetration or accumulation in the fetal compartment. Method: Ten paired amniotic fluid and maternal plasma samples were obtained during caesarian section for pharmacokinetic analysis. Antiretroviral concentrations were measured in both matrices using high-performance liquid chromatography (HPLC) and mass spectrometry (LC/MS) methodologies. Results: Median maternal plasma concentrations for NFV, M8, 3TC, and ZDV were 456, 244, 176, and 794 ng/mL, respectively, while median amniotic fluid concentrations were 118, 21, 2537, and 1483 ng/mL, respectively. The median NFV amniotic fluid to maternal plasma ratio was 0.44; the median M8 ratio was 0.11. Median 3TC and ZDV amniotic fluid to plasma ratios were 11.9 and 1.5, respectively. Conclusions: NFV and M8 exhibited partial drug transfer and/or accumulation in the amniotic compartment, whereas ZDV and 3TC concentrations mostly exceeded that in maternal plasma. Overall, all drugs achieved exposures in the amniotic fluid in excess of their wild-type viral susceptibilities. Amniotic fluid is an important compartment in the prevention of mother-to-child transmission; a further understanding of protease inhibitor and other antiretroviral drug penetration into amniotic fluid is warranted.  相似文献   
2.
端粒在肿瘤细胞和正常细胞中的表达量存在显著差异,并因此成为癌症治疗的主要靶点。随着对端粒酶抑制剂研究的深入,作为治疗艾滋病的核苷类逆转录酶抑制剂齐多夫定重新引起关注。本文综述齐多夫定作用于不同肿瘤细胞的体外研究进展。  相似文献   
3.
Zidovudine (AZT) is one of the most frequently used antiretroviral drugs in prevention of perinatal transmission of HIV. However, safety concerns on AZT use in pregnancy still persist as severe side effects are associated with AZT exposure in children. In our study we aimed to contribute to current knowledge on AZT transplacental transport and to evaluate potential involvement of the main human drug efflux ATP‐binding cassette (ABC) transporters, p‐glycoprotein (ABCB1), breast cancer resistance protein (ABCG2) and multidrug resistance‐associated proteins 2 and 5 (ABCC2 and ABCC5) in the disposition of AZT between mother and fetus. In order to elucidate this issue we investigated the effect of selected ABC transporters on AZT transepithelial transport across MDCKII cell monolayers. In addition we used the in situ method of dually perfused rat term placenta to further study the role of ABC transporters in AZT transplacental transport. In vitro studies revealed significant effect of ABCB1 and ABCG2 on AZT transport which was subsequently confirmed also on organ level. Lamivudine, an antiretroviral agent commonly co‐administered with AZT, did not affect ABC transporter‐mediated AZT transfer. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   
4.
Antiretroviral (ARV) drug therapy, given during pregnancy for prevention of mother‐to‐child transmission of human immunodeficiency virus 1 (HIV‐1), induces fetal mitochondrial dysfunction in some children. However, the persistence/reversibility of that dysfunction is unclear. Here we have followed Erythrocebus patas (patas) monkey offspring for up to 3 years of age (similar in development to a 15‐year old human) after exposure of the dams to human‐equivalent in utero ARV exposure protocols. Pregnant patas dams (3–5/exposure group) were given ARV drug combinations that included zidovudine (AZT)/lamivudine (3TC)/abacavir (ABC), or AZT/3TC/nevirapine (NVP), for the last 10 weeks (50%) of gestation. Infants kept for 1 and 3 years also received drug for the first 6 weeks of life. In offpsring at birth, 1 and 3 years of age mitochondrial morphology, examined by electron microscopy (EM), was compromised compared to the unexposed controls. Mitochondrial DNA (mtDNA), measured by hybrid capture chemiluminescence assay (HCCA) was depleted in hearts of patas exposed to AZT/3TC/NVP at all ages (< 0.05), but not in those exposed to AZT/3TC/ABC at any age. Compared to unexposed controls, mitochondrial reserve capacity oxygen consumption rate (OCR by Seahorse) in cultured bone marrow mesenchymal fibroblasts from 3‐year‐old patas offspring was ~50% reduced in AZT/3TC/ABC‐exposed patas (< 0.01), but not in AZT/3TC/NVP‐exposed patas. Overall the data show that 3‐year‐old patas sustain persistent mitochondrial dysfunction as a result of perinatal ARV drug exposure. Environ. Mol. Mutagen. 57:526–534, 2016. © 2016 Wiley Periodicals, Inc.  相似文献   
5.
The advent of highly active antiretroviral therapy has facilitated the virtual elimination of mother-to-child transmission of HIV infection in developed countries, reducing transmission rates to approximately 1 to 2%. In these settings, highly active antiretroviral therapy has also transformed pediatric HIV infection into a chronic disease; although there are associated costs in terms of side effects and the heavy pill burden. In less developed settings, easier-to-use adaptations of antiretroviral therapy regimens, such as short-course and single-dose antiretroviral strategies or neonatal postexposure prophylaxis can also substantially prevent mother-to-child transmission, although to a lesser degree than highly active antiretroviral therapy. However, postnatal transmission of infection through breastfeeding significantly reduces the longer-term efficacy of these strategies. Ongoing research is focusing on the use of antiretroviral therapy in the breastfeeding period.  相似文献   
6.
7.
目的:获得拉米夫定、齐多夫定以及两者混合物的太赫兹光谱,得到其频谱响应和折射率色散关系,从而进行定性定量分析。方法:利用太赫兹时域光谱技术测定拉米夫定、齐多夫定以及两者混合物,并用经典偏最小二乘回归方法建立模型对两者的混合物进行定性定量分析。结果:拉米夫定和齐多夫定在太赫兹波段都具有各自的特征吸收峰,说明利用太赫兹光谱可以将它们明显区分开来;其中校正集和验证集的相关系数均优于0.99,预测值的均方根误差小于1.2%。结论:根据太赫兹光谱包含的特征信息能够对该类药品混合物中的成分进行定性定量分析。  相似文献   
8.
9.
 目的高效液相色谱法同时测定齐多夫定和奈韦拉平血浆中的浓度。方法色谱柱为岛津Shim-pack CLC-ODS(6mm×15cm,5μm)。流动相为乙腈-水(23∶77),流速1mL·min-1。紫外检测波长为260nm。柱温为室温。内标物(替加氟)与齐多夫定、奈韦拉平的保留时间分别为4.665,5.198和10.912min。结果齐多夫定、奈韦拉平的线性范围分别为0.025~10mg·L-1(r=0.9999)和0.05~10mg·L-1(r=0.9999),最低检测下限分别为0.025和0.05mg·L-1。样品溶液冻融稳定,日内精密度和日间精密度良好,回收率较高。结论采用HPLC-UV测定血浆中齐多夫定和奈韦拉平浓度,方法简便,结果准确可靠。  相似文献   
10.
We report six HIV patients who developed painful periungual inflammation of several nails during treatment with the antiretroviral drugs indinavir and lamivudine. The lesions appeared 2-12 months after starting treatment. The occurrence of paronychia in HIV patients has recently been reported in two groups of patients receiving either indinavir or lamivudine. Dermatologists should be aware of this recently reported and probably not uncommon side-effect of antiretroviral treatment in order to avoid an invasive approach to the nail lesions.  相似文献   
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