Maternal-fetal transfer and amniotic fluid accumulation of nucleoside analogue reverse transcriptase inhibitors in human immunodeficiency virus-infected pregnant women
Maternal-fetal transfer and amniotic fluid accumulation of nucleoside analogue reverse transcriptase inhibitors in human immunodeficiency virus-infected pregnant women
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DOI：
10.1128/aac.48.11.4332-4336.2004
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发表时间：
2004-11-01
影响因子：
4.9
通讯作者：
Mandelbrot, L
中科院分区：
文献类型：
--
作者：
Chappuy, H;Tréluyer, JM;Mandelbrot, L
本研究旨在探讨核苷类似物逆转录酶抑制剂（NRTIs）在人类免疫缺陷病毒（HIV）感染孕妇体内的胎盘转移及其在羊水中的浓度。共有100名感染1型艾滋病毒的母亲在分娩时接受抗逆转录病毒治疗，包括一种或多种nrti，用于临床适应症。在分娩或剖宫产时采集母体血液和羊水，分娩后立即静脉穿刺采集配对脐带血。采用高效液相色谱法测定药物浓度。母体和脐带血浆样本中齐多夫定、拉米夫定、司他夫定和二腺苷的浓度存在显著关系。脐带血浆中齐多夫定及其葡萄糖醛酸代谢物（3′-叠氮-3′-脱氧胸腺嘧啶- β -d -葡萄糖醛酸）、司他夫定（R = 1.01）、拉米夫定（R = 0.93）和阿巴卡韦（R = 1.03）的浓度比值较高（R = 0.38）。羊水和脐带血浆中齐多夫定及其葡萄糖醛酸代谢物（R = 2.83）、司他夫定（R = 4.87）和拉米夫定（R = 3.99）的浓度比较高，二腺苷的浓度比较低（R = 1.14）。这些结果表明，大多数NRTIs通过简单扩散穿过胎盘，并可能通过胎儿尿排泄集中在羊水中。nrti的疗效或毒性可能因胎盘移植而异。
This study was performed to investigate placental transfer of nucleoside analogue reverse transcriptase inhibitors (NRTIs) and their concentrations in amniotic fluid when given to human immunodeficiency virus (HIV)-infected pregnant women. A total of 100 HIV type 1-infected mothers receiving antiretroviral therapy, including one or more NRTIs, for clinical indications at the time of delivery were enrolled. Maternal blood samples and amniotic fluid were obtained during delivery or cesarean section, and paired cord blood samples were obtained by venipuncture immediately after delivery. Drug concentrations were measured by using high-performance liquid chromatography. A significant relationship between concentrations in maternal and cord plasma samples was found for zidovudine, lamivudine, stavudine, and didanosine. The ratio between the concentrations in cord and maternal plasma samples (R) was high for zidovudine (R = 1.22), its glucuronide metabolite (3'-azido-3'-deoxythymidine-beta-D-glucuronide) (R = 1.01), stavudine (R = 1.32), lamivudine (R = 0.93), and abacavir (R = 1.03) and was low for didanosine (R = 0.38). The ratio between the concentrations in amniotic fluid and cord plasma samples was high for zidovudine (R = 2.24), its glucuronide metabolite (R = 2.83), stavudine (R = 4.87), and lamivudine (R = 3.99) and was lower for didanosine (R = 1.14). These findings indicate that most NRTIs cross the placenta by simple diffusion and are concentrated in the amniotic fluid, probably through fetal urinary excretion. The efficacy or toxicity of NRTIs may vary according to placental transfer.