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
善学以致用应助Mo采纳,获得10
刚刚
qq发布了新的文献求助10
1秒前
2秒前
3秒前
3秒前
爆米花应助成就茗采纳,获得10
5秒前
Akim应助15884134873采纳,获得10
5秒前
6秒前
roaring发布了新的文献求助10
6秒前
小屋完成签到,获得积分10
6秒前
8秒前
9秒前
10秒前
小屋发布了新的文献求助10
10秒前
11秒前
orixero应助roaring采纳,获得10
11秒前
张姐完成签到,获得积分10
11秒前
11秒前
842413119完成签到,获得积分10
12秒前
rrgogo发布了新的文献求助10
13秒前
直击灵魂完成签到 ,获得积分10
13秒前
醒醒完成签到,获得积分10
14秒前
张姐发布了新的文献求助10
14秒前
15秒前
15秒前
15秒前
15秒前
16秒前
15884134873发布了新的文献求助10
18秒前
俭朴的跳跳糖完成签到 ,获得积分10
18秒前
Mo完成签到,获得积分10
19秒前
tananna完成签到,获得积分10
19秒前
英俊的铭应助斯文念波采纳,获得10
19秒前
缥缈冬寒发布了新的文献求助10
20秒前
左肩微笑发布了新的文献求助10
21秒前
Rondab应助远山淡影_cy采纳,获得10
22秒前
yar应助张姐采纳,获得10
22秒前
CAOHOU应助张姐采纳,获得10
22秒前
Happyness应助张姐采纳,获得10
22秒前
24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 3989550
求助须知:如何正确求助?哪些是违规求助? 3531774
关于积分的说明 11254747
捐赠科研通 3270278
什么是DOI,文献DOI怎么找? 1804966
邀请新用户注册赠送积分活动 882125
科研通“疑难数据库(出版商)”最低求助积分说明 809176