Improved Predictability of Hepatic Clearance with Optimal pH for Acyl-Glucuronidation in Liver Microsomes.
Acyl-glucuronide
Carboxylic acid
Clearance
Glucuronidation
Intracellular pH
Optimal pH
buffer pH
microsome
Journal
Journal of pharmaceutical sciences
ISSN: 1520-6017
Titre abrégé: J Pharm Sci
Pays: United States
ID NLM: 2985195R
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
16
05
2022
revised:
30
07
2022
accepted:
11
08
2022
pubmed:
23
8
2022
medline:
19
10
2022
entrez:
22
8
2022
Statut:
ppublish
Résumé
The purpose of this study was to investigate the optimal pH for acyl-glucuronidation formation with carboxylic acid-containing compounds in human and rat liver microsomes to improve the predictability of their hepatic clearance. The optimal pH for acyl-glucuronidation of all 17 compounds was around pH 6.0 in human and rat liver microsomes. Correlation analysis was done with the predicted in vitro intrinsic clearance (CL
Identifiants
pubmed: 35995204
pii: S0022-3549(22)00350-1
doi: 10.1016/j.xphs.2022.08.015
pii:
doi:
Substances chimiques
Carboxylic Acids
0
Glucuronosyltransferase
EC 2.4.1.17
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3165-3173Informations de copyright
Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.