Role and Relevance of PEPT2 in Drug Disposition, Dynamics, and Toxicity

作者: Mohamed A. Kamal , Richard F. Keep , David E. Smith

DOI: 10.2133/DMPK.23.236

关键词:

摘要: Pept2 knockout mice are an important tool to evaluate the evolving role and relevance of this proton-coupled oligopeptide transporter beyond drug disposition, where also modulates pharmacodynamic toxicodynamic effects substrates. Our in vivo studies with glycylsarcosine have established “proof concept” that PEPT2 can a significant effect on dipeptide disposition. Subsequent aminocephalosporin antibiotic cefadroxil shown pharmacology infectious disease. Finally, endogenous peptidomimetic 5-aminolevulinic acid demonstrated toxicology framework porphyria- lead-induced neurotoxicity. These consistently dual action respect its apical localization choroid plexus epithelium kidney in: 1) effluxing substrates from CSF into plexus, thereby affecting regional pharmacokinetics brain; 2) reabsorbing renal tubular fluid proximal tubules, systemic exposure. Moreover, these limiting substrate concentrations is more dramatic than increasing In case acid, such modulation disposition translates directly changes

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