Imperial College London
Alternate

Dr David R Owen MD PhD

Faculty of Medicine, Department of Brain Sciences

Reader in Molecular Pharmacology and Experimental Medicine
 
 
 
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Contact

 

+44 (0)20 3313 6195d.owen Website

 
 
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Location

 

G20AICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Owen:2022:au.164659809.93631578/v1,
author = {Owen, D and Phillips, A and O'Connor, D and Grey, G and Aimola, L and Nicholas, R and Matthews, P},
doi = {au.164659809.93631578/v1},
journal = {British Journal of Clinical Pharmacology},
title = {Human pharmacokinetics of XBD173 and etifoxine distinguish their potential for pharmacodynamic effects mediated by TSPO},
url = {http://dx.doi.org/10.22541/au.164659809.93631578/v1},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:p id="p1">XBD173 and etifoxine are TSPO ligands that modulate inflammatoryresponses in preclinical models. Limited human pharmacokinetic data isavailable for either molecule, and the binding affinity of etifoxine forhuman TSPO is unknown. To allow for design of human challengeexperiments, we derived pharmacokinetic data for orally administeredetifoxine (50mg TDS) and XBD173 (90mg OD) and determined the bindingaffinity of etifoxine for TSPO. For XBD173, Cmax and free fractionmeasurements predicted a maximal free concentration of 1.1 nM, which issimilar to XBD173 binding affinity. For etifoxine, Cmax and freefraction measurements predicted a maximal free concentration of 0.31 nM,substantially lower than the Ki for etifoxine in human brain derivedhere (7.8uM, 95% CI 4.5-14.6uM). We conclude that oral XBD173 dosing at90mg OD will achieve pharmacologically relevant TSPO occupancy. However,the occupancy is too low for TSPO mediated effects after oral dosing ofetifoxine at 50mg TDS.</jats:p>
AU  - Owen,D
AU  - Phillips,A
AU  - O'Connor,D
AU  - Grey,G
AU  - Aimola,L
AU  - Nicholas,R
AU  - Matthews,P
DO  - au.164659809.93631578/v1
PY  - 2022///
SN  - 0306-5251
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/10.22541/au.164659809.93631578/v1
ER  -
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