Marzolini Catia, Rudin Christoph, Decosterd Laurent A, Telenti Amalio, Schreyer Alain, Biollaz Jérôme, Buclin Thierry
Division of Clinical Pharmacology, University Hospital of Lausanne, Lausanne, Switzerland.
AIDS. 2002 Apr 12;16(6):889-93. doi: 10.1097/00002030-200204120-00008.
Although combinations of different antiretroviral drugs are increasingly used by pregnant HIV-1-infected women, few human data are available to evaluate in utero protease inhibitors (PI) exposure. The aim of this study was to assess the extent of transplacental passage of PI at delivery.
Pregnant women treated with antiretroviral drugs including PI and/or nevirapine were eligible for the study. Placental transfer was determined by comparison of drug concentrations in blood samples simultaneously collected from a peripheral maternal vein and the umbilical cord at delivery. Drug levels were determined by high-performance liquid chromatography.
Thirteen maternal-cord blood sample pairs were evaluable for transplacental passage determination (nine nelfinavir, two ritonavir, one saquinavir, one lopinavir, two nevirapine). Median cord and maternal drug concentrations, respectively, were nelfinavir < 250 and 1110 ng/ml; ritonavir < 250 and 1113 ng/ml; saquinavir < 100 and 350 ng/ml; lopinavir < 250 and 3105 ng/ml and nevirapine 2072 and 2546 ng/ml. The cord-to-maternal blood ratio was extremely low for all PI.
PI do not cross the placenta to an appreciable extent and consequently cannot be expected to exert a direct antiviral activity in utero during the whole dosing interval. Limited transfer may result from their high degree of plasma protein binding and their backwards transport through P-glycoprotein, largely expressed in the placenta. In contrast, nevirapine readily crosses the placental barrier. Such considerations may support treatment decisions in pregnant women.
尽管感染HIV-1的孕妇越来越多地使用不同抗逆转录病毒药物的联合疗法，但几乎没有人体数据可用于评估子宫内蛋白酶抑制剂（PI）的暴露情况。本研究的目的是评估分娩时PI经胎盘转运的程度。
接受包括PI和/或奈韦拉平在内的抗逆转录病毒药物治疗的孕妇符合本研究条件。通过比较分娩时从母体外周静脉和脐带同时采集的血样中的药物浓度来确定胎盘转运情况。药物水平通过高效液相色谱法测定。
13对母血-脐血样本可用于胎盘转运测定（9对奈非那韦、2对利托那韦、1对沙奎那韦、1对洛匹那韦、2对奈韦拉平）。脐带血和母血中药物浓度的中位数分别为：奈非那韦<250和1110 ng/ml；利托那韦<250和1113 ng/ml；沙奎那韦<100和350 ng/ml；洛匹那韦<250和3105 ng/ml；奈韦拉平2072和2546 ng/ml。所有PI的脐带血与母血浓度比都极低。
PI在很大程度上不会穿过胎盘，因此在整个给药间隔期间，不能期望其在子宫内发挥直接抗病毒活性。其有限的转运可能是由于它们高度的血浆蛋白结合以及通过在胎盘中大量表达的P-糖蛋白的逆向转运。相比之下，奈韦拉平很容易穿过胎盘屏障。这些考虑因素可能有助于支持对孕妇的治疗决策。
