The Impact of Pregnancy on Antihypertensive Drug Metabolism and Pharmacokinetics: Current Status and Future Directions.
The Impact of Pregnancy on Antihypertensive Drug Metabolism and Pharmacokinetics: Current Status and Future Directions.
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DOI：
10.1080/17425255.2021.2002845
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发表时间：
2021-11
影响因子：
4.3
通讯作者：
Lee CR
中科院分区：
文献类型：
--
作者：
Mulrenin IR;Garcia JE;Fashe MM;Loop MS;Daubert MA;Urrutia RP;Lee CR
妊娠期高血压疾病（HDP）的患病率正在上升，并增加了不良母婴结局的风险。妊娠期间发生的生理变化会改变药物的药代动力学。然而，抗高血压药物缺乏妊娠特异性给药建议，这是由于围绕妊娠期抗高血压药物药代动力学变化程度和潜在机制的关键知识缺口。本综述（1）总结了目前推荐的非紧急HDP治疗的药物和给药策略，（2）回顾并综合了通过全面Pubmed检索识别的现有文献，评价了常用处方HDP药物的母体药代动力学的妊娠变化（特别是拉贝洛尔和硝苯地平），和（3）提供了深入了解代谢和清除机制改变HDP药物药代动力学在怀孕期间。最后总结了存在的知识差距和未来的研究方向。一系列小型药代动力学研究表明，妊娠期间拉贝洛尔和硝苯地平的口服清除率较高。药代动力学建模和临床前研究表明，这些效应可能是由于妊娠相关的肝脏UGT 1A 1和CYP 3A 4介导的首过代谢增加和生物利用度降低。因此，可能需要更高和/或更频繁的剂量来降低妊娠期间的血压。未来的研究需要解决各种证据缺口，并为开发更精确的抗高血压药物给药策略提供信息。
Hypertensive disorders of pregnancy (HDP) are rising in prevalence, and increase risk of adverse maternal and fetal outcomes. Physiologic changes occur during pregnancy that alter drug pharmacokinetics. However, antihypertensive drugs lack pregnancy-specific dosing recommendations due to critical knowledge gaps surrounding the extent of gestational changes in antihypertensive drug pharmacokinetics and underlying mechanisms. This review (1) summarizes currently recommended medications and dosing strategies for non-emergent HDP treatment, (2) reviews and synthesizes existing literature identified via a comprehensive Pubmed search evaluating gestational changes in the maternal pharmacokinetics of commonly prescribed HDP drugs (notably labetalol and nifedipine), and (3) offers insight into the metabolism and clearance mechanisms underlying altered HDP drug pharmacokinetics during pregnancy. Remaining knowledge gaps and future research directions are summarized. A series of small pharmacokinetic studies illustrate higher oral clearance of labetalol and nifedipine during pregnancy. Pharmacokinetic modeling and preclinical studies suggest these effects are likely due to pregnancy-associated increases in hepatic UGT1A1- and CYP3A4-mediated first-pass metabolism and lower bioavailability. Accordingly, higher and/or more frequent doses may be needed to lower blood pressure during pregnancy. Future research is needed to address various evidence gaps and inform the development of more precise antihypertensive drug dosing strategies.
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影响因子：
13.8
作者：
Butwick AJ;Druzin ML;Shaw GM;Guo N
通讯作者：
Guo N
影响因子：
3.4
作者：
Ayad M;Costantine MM
通讯作者：
Costantine MM
DOI：
10.1136/bmj.f6564
发表时间：
2013-11-07
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Ananth CV;Keyes KM;Wapner RJ
通讯作者：
Wapner RJ
影响因子：
7.2
作者：
通讯作者：
--
影响因子：
3.9
作者：
Chen, Huiqing;Yang, Kyunghee;Jeong, Hyunyoung
通讯作者：
Jeong, Hyunyoung