Alsmadi Mo'tasem M, Idkaidek Nasir
Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science & Technology, Irbid, Jordan.
College of Pharmacy, University of Petra, Amman, Jordan.
Curr Drug Metab. 2018;19(12):972-978. doi: 10.2174/1389200219666180702104034.
Clinical studies during pregnancy are rare due to ethical and practical limitations. Giving pregnant females the same dosing regimen used in adult males or nonpregnant females is inappropriate. Pregnancy physiologically-based pharmacokinetic modeling is a powerful tool that can be used to refine pharmacotherapy during pregnancy.
This work provides a review of the current status of application of physiologically based pharmacokinetic models in developing dosing regimens in pregnant women.
A structured search was done on Scholar Google, Science Direct and PubMed. The articles searched were those providing physiological, anatomical and biochemical data needed for pregnancy physiologically-based pharmacokinetic models or utilizing these models to evaluate the effect of pregnancy on drugs pharmacokinetics. Key words used for search include: PBPK and pregnancy, pharmacokinetic during pregnancy, ethics of pregnancy studies. The found articles were evaluated in terms of main pharmacokinetic features of the drug that were affected by pregnancy, the structure of the model, the software platform used and quality of predicted maternal and fetal exposure.
Pregnancy physiologically-based pharmacokinetic models can be used to optimize effective and safe dosing regimens needed during pregnancy. Different model structures have been successfully used for this purpose using different modeling software.
More work is needed to fill the gaps in knowledge needed to more accurately and mechanistically simulate simultaneous exposure of the pregnant mother and her fetus/ embryo to drugs using pregnancy physiologicallybased pharmacokinetic modeling approach.
由于伦理和实际限制，孕期临床研究很少见。给怀孕女性使用与成年男性或非怀孕女性相同的给药方案是不合适的。基于妊娠生理的药代动力学建模是一种强大的工具，可用于优化孕期药物治疗。
本文综述了基于生理的药代动力学模型在制定孕妇给药方案中的应用现状。
在谷歌学术、科学Direct和PubMed上进行了结构化搜索。搜索的文章是那些提供基于妊娠生理的药代动力学模型所需的生理、解剖和生化数据，或利用这些模型评估妊娠对药物药代动力学影响的文章。搜索使用的关键词包括：PBPK与妊娠、孕期药代动力学、妊娠研究伦理。根据受妊娠影响的药物主要药代动力学特征、模型结构、使用的软件平台以及预测的母体和胎儿暴露质量对找到的文章进行评估。
基于妊娠生理的药代动力学模型可用于优化孕期所需的有效和安全给药方案。不同的模型结构已成功用于此目的，使用了不同的建模软件。
需要开展更多工作来填补知识空白，以便使用基于妊娠生理的药代动力学建模方法更准确、更机械地模拟孕妇及其胎儿/胚胎同时暴露于药物的情况。
