Perfluoroalkyl substance excretion: Effects of organic anion-inhibiting and resin-binding drugs in a community setting.
Adult
Aged
Anticholesteremic Agents
/ therapeutic use
Cholestyramine Resin
/ therapeutic use
Environmental Pollutants
/ blood
Female
Fluorocarbons
/ blood
Humans
Male
Middle Aged
Organic Anion Transporters
/ antagonists & inhibitors
Probenecid
/ therapeutic use
Sulfonic Acids
/ blood
Uricosuric Agents
/ therapeutic use
Cholestyramine resin (MeSH) organic anion transporters (MeSH) antagonists and inhibitors (subheading)
Perfluoroalkyl substances (MeSH)
Perfluorohexane sulfonic acid
Perfluorononanoic acid
Perfluorooctane sulfonic acid
Perfluorooctanoic acid
Probenecid (MeSH)
Uricosuric agents (MeSH, pharmacologic action)
Journal
Environmental toxicology and pharmacology
ISSN: 1872-7077
Titre abrégé: Environ Toxicol Pharmacol
Pays: Netherlands
ID NLM: 9612020
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
18
01
2021
revised:
25
03
2021
accepted:
27
03
2021
pubmed:
6
4
2021
medline:
4
8
2021
entrez:
5
4
2021
Statut:
ppublish
Résumé
Longer serum half-lives of perfluoroalkyl substances (PFAS) in humans compared to other species has been attributed to differences in the activity of organic anion transporters (OAT). Among 56,175 adult participants in the community-based C8 Health Project, 23 subjects were taking the uricosuric OAT-inhibitor probenecid, and 36 subjects were taking the bile acid sequestrant cholestyramine. In regression models of log transformed serum PFAS, medication effects were estimated in terms of mean ratios, adjusting for age, gender, BMI, estimated glomerular filtration rate (eGFR) and water-district of residence. Probenecid was associated with modest, but not statistically significant increases in serum PFAS concentrations. In contrast, cholestyramine significantly lowered serum PFAS concentrations, notably for perfluorooctane sulfonic acid (PFOS). The effectiveness of cholestyramine in a community setting supports the importance of gastrointestinal physiology for PFAS excretion kinetics, especially for PFOS. We did not find clear evidence that probenecid, an inhibitor of OAT, affects PFAS clearance.
Sections du résumé
BACKGROUND
BACKGROUND
Longer serum half-lives of perfluoroalkyl substances (PFAS) in humans compared to other species has been attributed to differences in the activity of organic anion transporters (OAT).
METHODS
METHODS
Among 56,175 adult participants in the community-based C8 Health Project, 23 subjects were taking the uricosuric OAT-inhibitor probenecid, and 36 subjects were taking the bile acid sequestrant cholestyramine. In regression models of log transformed serum PFAS, medication effects were estimated in terms of mean ratios, adjusting for age, gender, BMI, estimated glomerular filtration rate (eGFR) and water-district of residence.
RESULTS
RESULTS
Probenecid was associated with modest, but not statistically significant increases in serum PFAS concentrations. In contrast, cholestyramine significantly lowered serum PFAS concentrations, notably for perfluorooctane sulfonic acid (PFOS).
CONCLUSIONS
CONCLUSIONS
The effectiveness of cholestyramine in a community setting supports the importance of gastrointestinal physiology for PFAS excretion kinetics, especially for PFOS. We did not find clear evidence that probenecid, an inhibitor of OAT, affects PFAS clearance.
Identifiants
pubmed: 33819618
pii: S1382-6689(21)00068-5
doi: 10.1016/j.etap.2021.103650
pii:
doi:
Substances chimiques
Anticholesteremic Agents
0
Environmental Pollutants
0
Fluorocarbons
0
Organic Anion Transporters
0
Sulfonic Acids
0
Uricosuric Agents
0
Cholestyramine Resin
11041-12-6
Probenecid
PO572Z7917
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103650Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.