Application of ultrasound-guided cholecystocentesis to the evaluation of the metabolite profiling in bile of dogs and cynomolgus monkeys.
biliary excretion
drug metabolism
preclinical models
Journal
Pharmacology research & perspectives
ISSN: 2052-1707
Titre abrégé: Pharmacol Res Perspect
Pays: United States
ID NLM: 101626369
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
23
04
2019
revised:
01
05
2019
accepted:
02
05
2019
entrez:
1
6
2019
pubmed:
1
6
2019
medline:
8
2
2020
Statut:
epublish
Résumé
In this study, we describe a novel approach for collecting bile from dogs and cynomolgus monkeys for metabolite profiling, ultrasound-guided cholecystocentesis (UCC). Sampling bile by UCC twice within 24 hours was well tolerated by dogs and monkeys. In studies with atorvastatin (ATV) the metabolite profiles were similar in bile obtained through UCC and from bile duct-cannulated (BDC) dogs. Similar results were observed in UCC and BDC monkeys as well. In both monkey and dog, the primary metabolic pathway observed for ATV was oxidative metabolism. The 2-hydroxy- and 4-hydroxyatorvastatin metabolites were the major oxidation products, which is consistent with previously published metabolite profiles. S-cysteine and glucuronide conjugates were also observed. UCC offers a viable alternative to bile duct cannulation for collection of bile for metabolite profiling of compounds that undergo biliary excretion, given the similar metabolite profiles in bile obtained via each method. Use of UCC for metabolite profiling may reduce the need for studies using BDC animals, a resource-intensive model.
Identifiants
pubmed: 31149343
doi: 10.1002/prp2.488
pii: PRP2488
pmc: PMC6536413
doi:
Substances chimiques
Glucuronides
0
Atorvastatin
A0JWA85V8F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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