Interpreting tacrolimus concentrations during pregnancy and postpartum.
Interpreting tacrolimus concentrations during pregnancy and postpartum.
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DOI：
10.1097/tp.0b013e318278d367
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发表时间：
2013-04-15
期刊：
影响因子：
6.2
通讯作者：
Easterling TR
中科院分区：
文献类型：
--
作者：
Hebert MF;Zheng S;Hays K;Shen DD;Davis CL;Umans JG;Miodovnik M;Thummel KE;Easterling TR
实体器官移植后妊娠，虽然被认为是高风险的产妇，胎儿和新生儿并发症，是相当成功的。妊娠期他克莫司药代动力学变化使得全血谷浓度的解释特别具有挑战性。有多种因素可增加未结合他克莫司的比例，包括但不限于低白蛋白浓度和低红细胞计数。将全血他克莫司谷浓度维持在常规治疗范围的临床剂量滴定可导致贫血和低白蛋白血症孕妇的未结合浓度升高并可能产生毒性。测量孕妇血浆或未结合的他克莫司浓度可能更好地反映药物的活性形式，尽管这些在技术上具有挑战性，而且在通常的临床实践中往往无法实现。他克莫司通过胎盘，子宫内接触量约为母体血液浓度的71%。胎儿血药浓度较低可能是由于他克莫司通过胎盘p -糖蛋白从胎儿向母体主动外排运输所致。迄今为止，他克莫司尚未与先天性畸形有关，但可引起新生儿可逆肾毒性和高钾血症。相反，极少量的他克莫司在母乳中排泄，不太可能引起哺乳婴儿的不良反应。
Pregnancy following solid organ transplantation, although considered high risk for maternal, fetal and neonatal complications, has been quite successful. Tacrolimus pharmacokinetic changes during pregnancy make interpretation of whole blood trough concentrations particularly challenging. There are multiple factors that can increase the fraction of unbound tacrolimus, including but not limited to low albumin concentration and low RBC count. The clinical titration of dosage to maintain whole blood tacrolimus trough concentrations in the usual therapeutic range can lead to elevated unbound concentrations and possibly toxicity in pregnant women with anemia and hypoalbuminemia. Measurement of plasma or unbound tacrolimus concentrations for pregnant women might better reflect the active form of the drug, though these are technically-challenging and often unavailable in usual clinical practice. Tacrolimus crosses the placenta with in utero exposure being approximately 71% of maternal blood concentrations. The lower fetal blood concentrations are likely due to active efflux transport of tacrolimus from the fetus toward the mother by placental P-glycoprotein. To date, tacrolimus has not been linked to congenital malformations, but can cause reversible nephrotoxicity and hyperkalemia in the newborn. In contrast, very small amounts of tacrolimus are excreted in the breast milk and are unlikely to elicit adverse effects in the nursing infant.