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• W2309585448 abstract "Previous pharmacokinetic studies of deltamethrin (DLM) have revealed that brain levels of this highly lipophilic pyrethroid insecticide are only 15-20% of plasma levels. Experiments were performed to assess determinants limiting CNS access including plasma protein binding and the efflux transporter, P-gp. A human brain microvascular endothelial cell line, hCMEC/D3, was utilized as a model in vitro system to evaluate blood-brain barrier (BBB) permeation. Incubation of DLM with a series of human serum albumin (HSA) concentrations showed that unbound (fu) DLM ranged from 80% with 0.01% HSA to ∼20% at the physiologically-relevant 4% HSA. A positive correlation (R=0.987) was seen between fu and cellular uptake. Concentration-dependent uptake of DLM in 0.01% HSA was non-linear and was reduced at 4°C and by the P-gp inhibitor cyclosporine (CSA), indicative of a specific transport process. Cellular accumulation of [(3)H]-paclitaxel, a P-glycoprotein (P-gp) substrate, was increased by CSA but not by DLM, suggesting that DLM is neither a substrate nor an inhibitor of P-gp. The concentration-dependent uptake of DLM from 4% HSA was linear and not significantly impacted by temperature or CSA. In situ brain perfusion studies monitoring brain association of DLM at 0.01% and 4% HSA confirmed the aforementioned in vitro findings. This study demonstrates that brain uptake of DLM under normal physiological conditions appears to be a passive, non-saturable process, limited by the high protein binding of the pyrethroid." @default.
• W2309585448 created "2016-06-24" @default.
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• W2309585448 date "2016-05-01" @default.
• W2309585448 modified "2023-09-23" @default.
• W2309585448 title "Plasma protein binding limits the blood brain barrier permeation of the pyrethroid insecticide, deltamethrin" @default.
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• W2309585448 doi "https://doi.org/10.1016/j.toxlet.2016.03.006" @default.
• W2309585448 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27016408" @default.
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