Increased coproporphyrin serum levels in healthy volunteers treated with the cholesterol uptake inhibitor ezetimibe.
Humans
Ezetimibe
/ administration & dosage
Coproporphyrins
/ blood
Healthy Volunteers
Rifampin
/ administration & dosage
Liver-Specific Organic Anion Transporter 1
/ metabolism
Male
Adult
Drug Interactions
Female
Anticholesteremic Agents
/ administration & dosage
Young Adult
Cholesterol
/ blood
Biomarkers
/ blood
HEK293 Cells
Middle Aged
Azetidines
Glucuronides
Journal
Clinical and translational science
ISSN: 1752-8062
Titre abrégé: Clin Transl Sci
Pays: United States
ID NLM: 101474067
Informations de publication
Date de publication:
Oct 2024
Oct 2024
Historique:
revised:
17
09
2024
received:
24
06
2024
accepted:
20
09
2024
medline:
9
10
2024
pubmed:
9
10
2024
entrez:
9
10
2024
Statut:
ppublish
Résumé
Ezetimibe undergoes glucuronidation that results in the active metabolite ezetimibe phenoxy-glucuronide (ezetimibe-glucuronide). This phase-II metabolite was shown to interact with the clinically relevant hepatic transporter organic anion transporting polypeptide (OATP) 1B1. In recent years, coproporphyrin I (CPI) was established as a Tier 1 biomarker for OATP1B-mediated interactions among other endogenous substrates like CPIII. To evaluate whether levels of the biomarker are affected by ezetimibe treatment, we assessed the impact of ezetimibe and ezetimibe-glucuronide on OATP1B1-mediated transport of CPs in vitro. Then, we quantified CP levels in serum samples of healthy volunteers treated with a single oral dose of ezetimibe (20 mg) alone or in combination with rifampin (600 mg). Results from our in vitro experiments showed a significant reduction in cellular CPI accumulation in the presence of ezetimibe-glucuronide with an IC
Substances chimiques
Ezetimibe
EOR26LQQ24
Coproporphyrins
0
Rifampin
VJT6J7R4TR
Liver-Specific Organic Anion Transporter 1
0
SLCO1B1 protein, human
0
coproporphyrin I
531-14-6
Anticholesteremic Agents
0
ezetimibe glucuronide
0
Cholesterol
97C5T2UQ7J
Biomarkers
0
Azetidines
0
Glucuronides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e70041Informations de copyright
© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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