Limited Impact of Murine Placental MDR1 on Fetal Exposure of Certain Drugs Explained by Bypass Transfer Between Adjacent Syncytiotrophoblast Layers

合胞滋养细胞 胎儿 药代动力学 地高辛 胎盘 化学 血脑屏障 分布(数学) 内分泌学 P-糖蛋白 内科学 药理学 男科 生物 医学 怀孕 多重耐药 中枢神经系统 生物化学 遗传学 数学分析 心力衰竭 抗生素 数学
作者
Arimi Fujita,Saki Noguchi,Rika Hamada,Satoko Inoue,Tsutomu Shimada,Satomi Katakura,Tetsuo Maruyama,Yoshimichi Sai,Tomohiro Nishimura,Masatoshi Tomi
出处
期刊:Pharmaceutical Research [Springer Science+Business Media]
卷期号:39 (7): 1645-1658 被引量:5
标识
DOI:10.1007/s11095-022-03165-6
摘要

Multidrug resistance protein 1 (MDR1) is located at the interface between two syncytiotrophoblast layers in rodent placenta, and may influence fetal drug distribution. Here, we quantitatively compare the functional impact per single MDR1 molecule of MDR1 at the placental barrier and blood-brain barrier in mice.MDR1A and MDR1B proteins were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Paclitaxel or digoxin was continuously administered to pregnant Mdr1a-/-/Mdr1b-/- or wild-type mice, and the drug concentrations in the maternal and fetal plasma and maternal brain were quantified by LC-MS/MS.MDR1A and MDR1B proteins are expressed in the membrane of mouse placental labyrinth, and total MDR1 at the placental barrier amounts to about 30% of that at the blood-brain barrier. The fetal-to-maternal plasma concentration ratio of digoxin was only marginally affected in Mdr1a-/-/Mdr1b-/- mice, while that of paclitaxel showed a several-fold increase. No such difference between the two drugs was found in the maternal brain distribution. The impact per single MDR1 molecule on the fetal distribution of digoxin was calculated to be much lower than that on the brain distribution, but this was not the case for paclitaxel. Our pharmacokinetic model indicates that the impact of placental MDR1 is inversely correlated to the ratio of permeability through gap junctions connecting the two syncytiotrophoblast layers to passive diffusion permeability.Our findings indicate that murine placental MDR1 has a minimal influence on the fetal concentration of certain substrates, such as digoxin, due to bypass transfer, probably via connexin26 gap junctions.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
领导范儿应助sssyq采纳,获得10
1秒前
1秒前
落寞的书易完成签到 ,获得积分10
2秒前
大方弘文发布了新的文献求助10
2秒前
2秒前
3秒前
谦让玲发布了新的文献求助10
3秒前
奇奇淼发布了新的文献求助10
3秒前
Lucas应助小田心采纳,获得10
4秒前
顺利紫山发布了新的文献求助10
4秒前
青春完成签到 ,获得积分10
4秒前
叶叶完成签到,获得积分10
5秒前
深情安青应助靓丽的发箍采纳,获得10
7秒前
壳米应助谦让玲采纳,获得10
10秒前
14秒前
上官若男应助哈哈哈哈采纳,获得10
14秒前
孙燕应助zhao采纳,获得30
14秒前
雪山完成签到,获得积分10
14秒前
14秒前
16秒前
谦让玲完成签到,获得积分10
16秒前
无花果应助讨厌科研采纳,获得10
17秒前
19秒前
19秒前
NexusExplorer应助hanleiharry1采纳,获得10
19秒前
21秒前
22秒前
23秒前
Owen应助八九采纳,获得10
25秒前
哈哈哈哈发布了新的文献求助10
25秒前
CAOHOU应助张wx_100采纳,获得10
25秒前
25秒前
Jasper应助东晓采纳,获得10
27秒前
成就宛完成签到,获得积分10
27秒前
29秒前
纯真的诗兰完成签到,获得积分10
29秒前
太渊完成签到 ,获得积分10
30秒前
31秒前
z2发布了新的文献求助10
31秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989390
求助须知:如何正确求助?哪些是违规求助? 3531487
关于积分的说明 11254109
捐赠科研通 3270153
什么是DOI,文献DOI怎么找? 1804887
邀请新用户注册赠送积分活动 882087
科研通“疑难数据库(出版商)”最低求助积分说明 809174