Imperial College London
Alternate

ProfessorRichardNicholas

Faculty of Medicine, Department of Brain Sciences

Professor of Practice (Neurology)
 
 
 
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r.nicholas

 
 
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Location

 

12L12CLab BlockCharing Cross Campus

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Summary

 

Publications

Citation

BibTex format

@article{Owen:2022:10.1111/bcp.15392,
author = {Owen, D},
doi = {10.1111/bcp.15392},
journal = {British Journal of Clinical Pharmacology},
pages = {4230--4236},
title = {Human pharmacokinetics of XBD173 and etifoxine distinguish their potential for pharmacodynamic effects mediated by TSPO},
url = {http://dx.doi.org/10.1111/bcp.15392},
volume = {88},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - XBD173 and etifoxine are translocator protein (TSPO) ligands that modulate inflammatory responses in preclinical models. Limited human pharmacokinetic data is available for either molecule, and the binding affinity of etifoxine for human TSPO is unknown. To allow for design of human challenge experiments, we derived pharmacokinetic data for orally administered etifoxine (50 mg 3 times daily) and XBD173 (90 mg once daily) and determined the binding affinity of etifoxine for TSPO. For XBD173, maximum plasma concentration and free fraction measurements predicted a maximal free concentration of 1.0 nM, which is similar to XBD173 binding affinity. For etifoxine, maximum plasma concentration and free fraction measurements predicted a maximal free concentration of 0.31 nM, substantially lower than the Ki for etifoxine in human brain derived here (7.8 μM, 95% CI 4.5–14.6 μM). We conclude that oral XBD173 dosing at 90 mg once daily will achieve pharmacologically relevant TSPO occupancy. However, the occupancy is too low for TSPO mediated effects after oral dosing of etifoxine at 50 mg 3 times daily.
AU  - Owen,D
DO  - 10.1111/bcp.15392
EP  - 4236
PY  - 2022///
SN  - 0306-5251
SP  - 4230
TI  - Human pharmacokinetics of XBD173 and etifoxine distinguish their potential for pharmacodynamic effects mediated by TSPO
T2  - British Journal of Clinical Pharmacology
UR  - http://dx.doi.org/10.1111/bcp.15392
UR  - https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15392
UR  - http://hdl.handle.net/10044/1/97016
VL  - 88
ER  -
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