Pacifici G M, Nottoli R
Department of Biomedicine, University of Pisa, Medical School, Italy.
Clin Pharmacokinet. 1995 Mar;28(3):235-69. doi: 10.2165/00003088-199528030-00005.
Drugs administered to mothers have the potential to cross the placenta and reach the fetus. Under particular circumstances, the comparison of the drug concentration in the maternal and fetal plasma may give an idea of the exposure of the fetus to the maternally administered drugs. In this review drugs are classified according to their type of transfer across the placenta. Several drugs rapidly cross the placenta and pharmacologically significant concentrations equilibrate in maternal and fetal plasma. Their transfer is termed 'complete'. Other drugs cross the placenta incompletely, and their concentrations are lower in the fetal than in maternal plasma. The majority of drugs fit into 1 of these 2 groups. A limited number of drugs reach greater concentrations in fetal than maternal plasma. It is said that these drugs have an 'exceeding' transfer. The impression prevails that suxamethonium chloride (succinylcholine chloride) and doxorubicin do not cross the placenta. However, a careful analysis of the literature suggests that this impression is wrong and that all drugs cross the placenta, although the extent transfer varies considerably. The following parameters were considered as possible factors determining the extent of placental transfer: (i) the molecular weight of the drug; (ii) the pKa (pH at which the drug is 50% ionised); and (iii) the extent of drug binding to the plasma protein. Drugs with molecular weights greater than 500D have an incomplete transfer across the human placenta. Strongly dissociated acid drug molecules should have an incomplete transfer, but this does not seem to be an absolute rule. For example, ampicillin and methicillin transfer completely and they are strongly dissociated at physiological pH. The extent of drug binding to plasma protein does not influence the type of drug transfer across the human placenta.
给予母亲的药物有可能穿过胎盘并到达胎儿体内。在特定情况下，比较母体和胎儿血浆中的药物浓度可以了解胎儿接触母体给药的情况。在本综述中，药物根据其穿过胎盘的转移类型进行分类。几种药物能迅速穿过胎盘，母体和胎儿血浆中的药理有效浓度达到平衡。它们的转移被称为“完全”转移。其他药物穿过胎盘不完全，胎儿体内的浓度低于母体血浆中的浓度。大多数药物属于这两组中的一组。少数药物在胎儿体内的浓度高于母体血浆中的浓度。据说这些药物有“超越性”转移。普遍的印象是氯化琥珀胆碱（琥珀酰胆碱）和阿霉素不会穿过胎盘。然而，对文献的仔细分析表明这种印象是错误的，所有药物都会穿过胎盘，尽管转移程度差异很大。以下参数被认为是决定胎盘转移程度的可能因素：（i）药物的分子量；（ii）pKa（药物50%离子化时的pH值）；以及（iii）药物与血浆蛋白结合的程度。分子量大于500D的药物在人胎盘上的转移不完全。强解离的酸性药物分子应该有不完全转移，但这似乎不是绝对规律。例如，氨苄西林和甲氧西林完全转移，它们在生理pH值下强烈解离。药物与血浆蛋白结合的程度不影响药物在人胎盘上的转移类型。
