Increased penetration of diphenhydramine in brain via proton-coupled organic cation antiporter in rats with lipopolysaccharide-induced inflammation

Uptake transporters in brain microvascular endothelial cells (BMECs) are involved the penetration of basic (cationic) drugs such as diphenhydramine (DPHM) into brain. Lipopolysaccharide (LPS)-induced inflammation alters expression levels and activities uptake transporters, which change DPHM A microdialysis study showed that unbound brain-to-plasma partition coefficient ( K p,uu,brain ) for LPS rats was approximately two times higher than control rats. The transcellular transport to BMECs increased when were cultured with serum from Compared or BMECs, intracellular accumulation under a high pH rats, respectively. Treatment transporter inhibitors inflammatory cytokines had little impact on BMECs. This suggests LPS-induced promotes unidentified proton-coupled organic cation (H + /OC) antiporters improve rat via blood-brain barrier. • lipopolysaccharide-induced promoted by treatments inflammation. DPHM.