Department of Occupational and Environmental Health, School of Public Health, West Virginia University, Morgantown, WV, United States; Department of Medicine, School of Medicine, West Virginia University, United States.
Department of Occupational and Environmental Health, School of Public Health, West Virginia University, Morgantown, WV, United States; Department of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, WV, United States; MI Lust Associates, LLC, Morgantown, WV, United States.
Environ Toxicol Pharmacol. 2021 Jul;85:103650. doi: 10.1016/j.etap.2021.103650. Epub 2021 Apr 2.
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.
与其他物种相比,人体内全氟烷基物质 (PFAS) 的血清半衰期更长,这归因于有机阴离子转运蛋白 (OAT) 的活性差异。
在基于社区的 C8 健康项目的 56175 名成年参与者中,23 名参与者正在服用促进尿酸排泄的 OAT 抑制剂丙磺舒,36 名参与者正在服用胆汁酸螯合剂考来烯胺。在血清 PFAS 的对数转换回归模型中,根据平均比值估计药物效应,调整年龄、性别、BMI、估计肾小球滤过率 (eGFR) 和居住地区。
丙磺舒与血清 PFAS 浓度的适度但无统计学意义的增加相关。相比之下,考来烯胺显著降低了血清 PFAS 浓度,特别是对全氟辛烷磺酸 (PFOS)。
考来烯胺在社区环境中的有效性支持了胃肠道生理学对 PFAS 排泄动力学的重要性,特别是对 PFOS。我们没有发现明确的证据表明 OAT 抑制剂丙磺舒会影响 PFAS 的清除。