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In-vitro and in situ assessment of the efflux of five antidepressants by breast cancer resistance protein

Authors :
Suqin Feng
Ling Wang
Xuehua Jiang
Shiwei Tang
Liang Zheng
Gu Juan
Source :
The Journal of pharmacy and pharmacology. 71(7)
Publication Year :
2018

Abstract

Objectives Antidepressants need to penetrate the blood–brain barrier (BBB) to exert their functions in the central nervous system. Breast cancer resistance protein (BCRP), an efflux transporter abundantly expressed in the BBB, prevents the accumulation of many drugs in the brain. This study aimed to identify whether five commonly used antidepressants (sertraline, duloxetine, fluoxetine, amitriptyline and mirtazapine) are BCRP substrates. Methods A combination of bidirectional transport and intracellular accumulation experiments was conducted on BCRP-overexpressing MDCKII and wild-type (WT) cells, and in situ brain perfusion was conducted in rats. Key findings The bidirectional transport study revealed that the net efflux ratio (NER) of sertraline reached 2.08 but decreased to 1.06 when co-incubated with Ko143, a selective BCRP inhibitor. Conversely, the other four antidepressants did not appear to be BCRP substrates, due to their low NER values ( Conclusions Taken together, BCRP is involved in sertraline efflux.

Details

ISSN :
20427158
Volume :
71
Issue :
7
Database :
OpenAIRE
Journal :
The Journal of pharmacy and pharmacology
Accession number :
edsair.doi.dedup.....b17641b1b6eb701afe97b5f4cb824afc