P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies: A Case-Reference Study.
P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies: A Case-Reference Study.
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DOI：
10.1007/s40264-015-0299-3
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发表时间：
2015-07
期刊：
影响因子：
4.2
通讯作者：
Wilffert, Bob
中科院分区：
文献类型：
--
作者：
Daud, Aizati N. A.;Bergman, Jorieke E. H.;Bakker, Marian K.;Wang, Hao;Kerstjens-Frederikse, Wilhelmina S.;de Walle, Hermien E. K.;Groen, Henk;Bos, Jens H. J.;Hak, Eelko;Wilffert, Bob
怀孕期间使用药物是非常常见的，但可能会对胎儿造成伤害。药物的致畸作用部分取决于胎儿循环中的药物水平，这与通过胎盘的运输有关。许多药物是P-糖蛋白（P-gp）的底物，P-糖蛋白是一种外排转运蛋白，可作为胎儿的保护屏障。我们的目的是确定是否与P-gp相关的药物相互作用促进胎儿药物暴露的任何变化，如测量的风险有先天性异常的儿童。在本研究中，病例（N = 4634）为EUROCAT北方荷兰登记处登记的先天性异常儿童的母亲，参考人群为药物处方数据库（IADB.nl）中儿童的母亲（N = 25，126）。与P-gp转运相关的药物通常用于妊娠病例（10%）和人群（12%）。几种药物类别，这是底物的P-gp，被证明有较高的用户率的情况下，母亲与特定的异常。该药物子集与其他P-gp底物联合使用增加了特定异常的风险（比值比[OR] 4.17，95% CI 1.75-9.91），添加抑制剂进一步增加了风险（OR 13.03，95% CI 3.37-50.42）。当根据底物特异性分别分析药物时，观察到相同的风险增加模式。妊娠期间使用与P-gp转运相关的药物很常见。对于与特定异常相关的几种药物类别，P-gp介导的药物相互作用与这些特定异常的风险增加相关。本文的在线版本（doi：10.1007/s40264-015-0299-3）包含补充材料，可供授权用户使用。
Drug use in pregnancy is very common but may cause harm to the fetus. The teratogenic effect of a drug is partly dependent on the drug level in the fetal circulation, which is associated with the transport across the placenta. Many drugs are substrates of P-glycoprotein (P-gp), an efflux transporter that acts as a protective barrier for the fetus. We aim to identify whether drug interactions associated with P-gp promote any changes in fetal drug exposure, as measured by the risk of having children with congenital anomalies. In this study, cases (N = 4634) were mothers of children with congenital anomalies registered in the EUROCAT Northern Netherlands registry, and the reference population were mothers of children (N = 25,126) from a drug prescription database (IADB.nl). Drugs that are associated with P-gp transport were commonly used in pregnancy in cases (10 %) and population (12 %). Several drug classes, which are substrates for P-gp, were shown to have a higher user rate in mothers of cases with specific anomalies. The use of this subset of drugs in combination with other P-gp substrates increased the risk for specific anomalies (odds ratio [OR] 4.17, 95 % CI 1.75–9.91), and the addition of inhibitors further increased the risk (OR 13.03, 95 % CI 3.37–50.42). The same pattern of risk increment was observed when the drugs were analyzed separately according to substrate specificity. The use of drugs associated with P-gp transport was common during pregnancy. For several drug classes associated with specific anomalies, P-gp-mediated drug interactions are associated with an increased risk for those specific anomalies. The online version of this article (doi:10.1007/s40264-015-0299-3) contains supplementary material, which is available to authorized users.
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