Transfer of zidovudine (AZT) by human placenta.
Transfer of zidovudine (AZT) by human placenta.
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通过人胎盘转移齐多夫定 (AZT)。
DOI：
10.1093/infdis/161.2.203
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Dancis,J
中科院分区：
文献类型：
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作者：
Liebes,L;Mendoza,S;Wilson,D;Dancis,J
采用独立母胎循环的体外灌注系统研究了齐多夫定（AZT）在人胎盘中的转移。AZT向胎儿转移的速度比l -葡萄糖更快（转移指数1.5），这是一种比AZT更小的水溶性分子（267比180Da），被动地扩散穿过胎盘。在0.03-300µM范围内，转移率与母体灌注液浓度成正比。向母体灌注的相反方向的转移速率也超过了l -葡萄糖的转移速率，未能表现出饱和性。这些观察结果与简单扩散一致。灌注缓冲液与辛醇之间AZT和葡萄糖的分割率分别为1.04和0.013，说明AZT具有更强的亲脂性，这也为AZT更快的转移提供了合理的解释。AZT被胎盘广泛代谢为极性更强且尚未识别的代谢物，这些代谢物不会释放到灌注液中。这些代谢物的胎盘积累可能发挥抗病毒作用，也可能影响胎盘功能，这一可能性必须加以考虑。
The transfer of zidovudine (AZT) across human placenta was studied using an in vitro perfusion system with independent maternal and fetal circulations. AZT is transferred toward the fetus more rapidly thanL-glucose (transfer index 1.5), a water-soluble molecule smaller than AZT(267 vs. 180Da) that passively diffuses across the placenta. The transfer rate is proportional to the concentration in the maternal perfusate over a range of 0.03–300 µM. Transfer rate in the reverse direction, toward the maternal perfusate, also exceeds that ofL-glucose and fails to show saturability. These observations are consistent with simple diffusion. The partition ofAZT and glucose between perfusion buffer and octanol is 1.04 and 0.013, respectively, indicating that AZT is more lipophilic and providing a reasonable explanation for the more rapid transfer. AZT is extensively metabolized by the placenta to more polar and as yet unidentified metabolites that are not released into the perfusate. The possibility that the placental accumulation of such metabolite(s) may exert an antiviral action and may also affect placental function must be considered.