Transfer of dideoxyinosine across the human isolated placenta.
Transfer of dideoxyinosine across the human isolated placenta.
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双脱氧肌苷穿过人分离胎盘的转移。
DOI：
10.1111/j.1365-2125.1994.tb04347.x
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发表时间：
1994
影响因子：
3.4
通讯作者：
Schenker,S
中科院分区：
文献类型：
--
作者：
Henderson,GI;Perez,AB;Yang,Y;Hamby,RL;Schenken,RS;Schenker,S
1.双脱氧肌苷（ddI）最近被批准用于治疗HIV感染患者。随着越来越多的此类患者怀孕，我们希望确定胎盘向胎儿转移DDI的速率和机制。使用分离的单灌注的人类足月胎盘子叶，药物被证明可以以自由扩散标记安替比林的25%的速率和齐多夫定（AZT）的大约一半的速率从母体到胎儿穿过胎盘。ddI的转移在两个方向（母体到胎儿和相反方向）上相似，与L-葡萄糖（一种被动转运的糖）的转移相同，并且不受过量肌苷或尿酸（ddI的结构类似物）的抑制。ddI没有逆着浓度梯度穿过胎儿。转运过程似乎是被动的，AZT不改变转运过程。2. ddI在Krebs Ringer缓冲液/白蛋白灌注液中没有代谢，胎盘匀浆在4小时孵育期间仅将4%的ddI转化为次黄嘌呤。然而，当母体足月或脐带血与DDI孵育3小时，50%的药物转化为次黄嘌呤在母体血液和次黄嘌呤和尿酸在脐带血。3.因此，母体血液中的DDI代谢应减少其体内向胎儿的净转移。在胎儿循环中，ddI将被红细胞进一步代谢为次黄嘌呤，并可能代谢为尿酸。因此，给予的ddI递送到胎儿组织的分数应远低于AZT。
1. Dideoxyinosine (ddI) has recently been approved for the treatment of patients with HIV infection. As increasing numbers of such patients are pregnant, we wished to define the rate and mechanism(s) of ddI transfer by the placenta to the foetus. Using isolated single perfused human term placental cotyledons, the drug was shown to cross the placenta from mother to foetus at a rate of 25% that of a freely diffusible marker, antipyrine, and at about half the rate of zidovudine (AZT). The transfer of ddI was similar in both directions (maternal to foetal and the reverse), equal to that of L‐glucose, a passively transported sugar, and was not inhibited by excess inosine or uric acid (structural analogues of ddI). ddI did not cross to the foetus against a concentration gradient. The transport process appeared to be passive and it was not altered by AZT. 2. ddI was not metabolized in the Krebs Ringer buffer/albumin perfusate, and placental homogenates converted only 4% of ddI to hypoxanthine over the 4 h incubation. However, when maternal term or cord blood was incubated with ddI for 3 h, 50% of the drug was converted to hypoxanthine in maternal blood and to hypoxanthine and uric acid in cord blood. 3. Thus, ddI metabolism in maternal blood should decrease its net transfer to the foetus in vivo. In the foetal circulation, ddI will be further metabolized by erythrocytes to hypoxanthine and possibly to uric acid. Hence, the fraction of administered ddI delivered to foetal tissues should be much lower than that of AZT.