哺乳期生理药代动力学模型的研究及应用现状

Research and application status of physiologically based pharmacokinetic model during lactation

母乳喂养是婴儿出生后喂养的最佳形式,对婴儿的健康发育十分重要。目前临床上存在母亲用药导致婴儿出现毒性反应的病例,且大多数药物缺乏关于母乳喂养期间用药安全性的信息,这导致尽管很多药物可能是安全的,哺乳期女性仍然选择终止治疗或停止喂养。为了鼓励母乳喂养,需要在母亲开始母乳喂养或药物治疗之前进行药物治疗风险评估。不幸的是,由于人类哺乳期研究受限较大,目前的临床数据匮乏,而以体外和动物模型为主的实验数据也并不能完全拟合人体生理。因此,经过验证的非临床方法——基于生理学的药代动力学(PBPK)模型可能是一种有效的方法,预测药物转移到母乳中的程度,填补这一领域的信息空白。本文概述了哺乳期的用药现状、体内外研究现状和方法,以及哺乳期PBPK模型的研究实例。PBPK模型在哺乳期药物研究中意义重大,今后的发展应整合现有模型及相关数据,结合实际情况选择合适的模型,不断提高哺乳期PBPK模型对临床常用药物预测的准确性。

Breastfeeding is the best form of feeding after birth,which is very important for the growth of infants.At present,there are cases of toxic reactions in infants caused by mothers’drug use,and most drugs lack information on the safety of drug use during breastfeeding,which leads to that although many drugs may be safe,lactating women still choose to terminate treatment or stop feeding.In order to encourage breastfeeding,a risk assessment of medication needs to be conducted before the mother begins breastfeeding or medication.Unfortunately,due to the great limitation of human lactation research,the current clinical data is scarce,and the experimental data mainly based on in vitro and animal models cannot fully fit human physiology.Therefore,the validated non clinical method-physiologically based pharmacokinetic(PBPK)model may be an effective method to predict the extent of drug transfer to breast milk and fill the information gap in this field.In this paper,the current situation of drug use in lactation,the research status and methods in vivo and in vitro,and the research examples of PBPK model in lactation were summarized.The PBPK model is of great significance in the research of lactating drugs.The future development should integrate the existing models and relevant data,select the appropriate model in combination with the actual situation,and constantly improve the accuracy of the PBPK model in the prediction of commonly used clinical drugs.