Maternal-Fetal Transport of Hypoglycaemic Drugs
Maternal-Fetal Transport of Hypoglycaemic Drugs
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DOI：
10.2165/00003088-200342040-00001
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发表时间：
2003-01-01
影响因子：
4.000
通讯作者：
Gideon Koren
中科院分区：
文献类型：
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作者：
Facundo Garcia-Bournissen;Denice S. Feig;Gideon Koren
由于法律的、伦理和金钱问题，妊娠期药物研究很少。妊娠期间发生的许多药代动力学和药效学变化可能会影响药物的疗效和安全性，如果没有适当的研究，这些变化很难预测。在妊娠期可能有用和安全的药物必须在临床相关浓度下不穿过胎盘和/或对胎儿无害。第一个特征可以使用<i>体外</i>模型如胎盘灌注模型来预测。在格列本脲（格列本脲）的情况下，<i>体外</i>实验显示最小的母胎转移，导致完成了一个成功的临床试验，这种药物在妊娠糖尿病。胰岛素是治疗妊娠期糖尿病的主要药物，<i>在体外</i>也被证明不能穿过胎盘，赖脯胰岛素也是如此。当与抗胰岛素抗体复合时，动物胰岛素可穿过胎盘。其他磺酰脲类药物（甲苯磺丁脲和氯磺丙脲）<i>在体外</i>和<i>体内</i>均显示可穿过胎盘，并对胎儿产生毒性。本文综述了妊娠期降糖药物的药代动力学数据，以及<i>体外</i>胎盘灌注模型在妊娠期潜在有用药物临床前评价中的潜在作用。
Due to legal, ethical and monetary problems, drug studies in pregnancy are rare. Numerous pharmacokinetic and pharmacodynamic changes occur in pregnancy that can affect the efficacy and safety of drugs, and these are difficult to predict without appropriate studies. Drugs potentially useful and safe in pregnancy have to either not cross the placenta and/or be harmless to the fetus at clinically relevant concentrations. The first characteristic can be predicted using <i>in vitro</i> models such as the placenta perfusion model. In the case of glibenclamide (glyburide), <i>in vitro</i> experiments showed minimal maternal-fetal transfer, leading to completion of a successful clinical trial of this drug in gestational diabetes. Insulin, the main drug used in diabetes during pregnancy, has also been shown not to cross the placenta <i>in vitro</i> , as has insulin lispro. Animal insulin may cross the placenta when complexed with anti-insulin antibodies. Other sulphonylurea drugs (tolbutamide and chlorpropamide) have been shown to cross the placenta both <i>in vitro</i> and <i>in vivo</i> and to produce toxicity in the fetus. This review summarises the pharmacokinetic data available for hypoglycaemic drugs during pregnancy, as well as the potential role for the <i>in vitro</i> placenta perfusion model in the preclinical evaluation of drugs with potential usefulness in pregnancy.