Imperial College London
Alternate

ProfessorIanWilson

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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i.wilson

 
 
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Location

 

311Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Molloy:2023:10.1080/00498254.2023.2179952,
author = {Molloy, BJ and King, A and Gethings, LA and Plumb, RS and Mortishire-Smith, RJ and Wilson, ID},
doi = {10.1080/00498254.2023.2179952},
journal = {Xenobiotica: the fate of foreign compounds in biological systems},
pages = {93--105},
title = {Investigation of the pharmacokinetics and metabolic fate of Fasiglifam (TAK-875) in male and female rats following oral and intravenous administration},
url = {http://dx.doi.org/10.1080/00498254.2023.2179952},
volume = {53},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The metabolism and pharmacokinetics of fasiglifam (TAK-875, 2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid), a selective free fatty acid receptor 1 (FFAR1)/GPR40 agonist, were studied following intravenous (5 mg/kg) and oral administration (10 and 50 mg/kg) to male and female Sprague Dawley rats.Following intravenous dosing at 5 mg/kg, peak observed plasma concentrations of 8.8/9.2 µg/ml were seen in male and female rats respectively.Following oral dosing, peak plasma concentrations at 1 h of ca. 12.4/12.9 µg/ml for 10 mg/kg and 76.2/83.7 µg/ml for 50 mg/kg doses were obtained for male and female rats respectively. Drug concentrations then declined in the plasma of both sexes with t1/2’s of 12.4 (male) and 11.2 h (female). Oral bioavailability was estimated to be 85-120% in males and females at both dose levels.Urinary excretion was low, but in a significant sex-related difference, female rats eliminated ca. 10-fold more drug-related material by this route.Fasiglifam was the principal drug-related compound in plasma, with 15 metabolites, including the acyl glucuronide, also detected. In addition to previously identified metabolites, a novel biotransformation, that produced a side-chain shortened metabolite via elimination of CH2 from the acetyl side chain was noted with implications for drug toxicity.
AU  - Molloy,BJ
AU  - King,A
AU  - Gethings,LA
AU  - Plumb,RS
AU  - Mortishire-Smith,RJ
AU  - Wilson,ID
DO  - 10.1080/00498254.2023.2179952
EP  - 105
PY  - 2023///
SN  - 0049-8254
SP  - 93
TI  - Investigation of the pharmacokinetics and metabolic fate of Fasiglifam (TAK-875) in male and female rats following oral and intravenous administration
T2  - Xenobiotica: the fate of foreign compounds in biological systems
UR  - http://dx.doi.org/10.1080/00498254.2023.2179952
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000935482000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://www.tandfonline.com/doi/full/10.1080/00498254.2023.2179952
UR  - http://hdl.handle.net/10044/1/105287
VL  - 53
ER  -
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