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Purpose To develop a semi-mechanistic population pharmacokinetic (PK) model to quantitate the disposition kinetics of L-histidine, a peptide-histidine transporter 1 (PHT1) substrate, in the plasma, cerebrospinal fluid and brain parenchyma of wildtype (WT) and Pht1 knockout (KO) mice. Methods L-[14C]Hisidine (L-His) was administrated to WT and KO mice via tail vein injection, after which plasma,...
PHT1 (SLC15A4) is responsible for translocating l-histidine (l-His), di/tripeptides and peptide-like drugs across biological membranes. Previous studies have indicated that PHT1 is located in brain parenchyma, however, its role and significance in brain along with effect on the biodistribution of substrates is unknown. In this study, adult gender-matched Pht1-competent (wildtype) and Pht1-deficient...
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