Pharmacokinetics of Tropifexor, a Potent Farnesoid X Receptor Agonist, in Participants With Varying Degrees of Hepatic Impairment.
FXR agonist
hepatic impairment
nonalcoholic fatty liver diseases
pharmacokinetics
tropifexor
Journal
Journal of clinical pharmacology
ISSN: 1552-4604
Titre abrégé: J Clin Pharmacol
Pays: England
ID NLM: 0366372
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
14
09
2021
accepted:
28
10
2021
pubmed:
6
11
2021
medline:
19
4
2022
entrez:
5
11
2021
Statut:
ppublish
Résumé
Tropifexor, a non-bile acid farnesoid X receptor (FXR) agonist, has dose-proportional pharmacokinetics and no obvious major enterohepatic circulation. This open-label study investigated the effect of hepatic impairment (HI), as determined by Child-Pugh grade, on tropifexor's pharmacokinetics, safety, and tolerability following a 200-μg dose in the fasted state. Blood samples were collected through 168 hours after dosing for quantification and plasma protein-binding determination. Total tropifexor exposure was comparable across participants with HI vs those with normal hepatic function. Tropifexor was highly protein bound (>99%) in human plasma across participants of all groups. The average unbound fractions (percentage free) were 0.14% in participants with normal hepatic function and mild HI, which increased to 0.17% and 0.24% in participants with moderate and severe HI, respectively. Similar unbound drug exposure was noted in participants with mild HI and normal hepatic function. Participants with moderate HI (N = 8) had a 1.6-fold increase in unbound exposure (area under the plasma concentration-time curve from time 0 to infinity [AUC
Substances chimiques
Benzothiazoles
0
Isoxazoles
0
tropifexor
NMZ08KM76Z
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
520-531Informations de copyright
© 2021, The American College of Clinical Pharmacology.
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