Sertraline inhibits the transport of PAT1 substratesin vivoandin vitro

摘要: Background and Purpose Intestinal nutrient transporters may mediate the uptake of drugs. The aim this study was to investigate whether sertraline interacts with intestinal proton-coupled amino acid transporter 1 PAT1 (SLC36A1). Experimental Approach In vitro investigations interactions between human (h)PAT1, hSGLT1 (sodium-glucose linked 1) hPepT1 (proton-coupled di-/tri-peptide were conducted in Caco-2 cells using radiolabelled substrates. In vivo pharmacokinetic male Sprague–Dawley rats gaboxadol (10 mg·kg−1, p.o.) as a substrate (0–30.6 mg·kg−1). Gaboxadol quantified by hydrophilic interaction chromatography followed MS/MS detection. Key Results Sertraline inhibited hPAT1-mediated L-[3H]-Pro cells. This appeared be non-competitive. [14C]-α–methyl-D-glycopyranoside [14C]-Gly-Sar also decreased presence 0.3 mM sertraline. rats, administration (0.1–10 mM, corresponding 0.3–30.6 mg·kg−1, significantly reduced maximal plasma concentration AUC after its p.o. Conclusions Implications Sertraline is an apparent non-competitive inhibitor transport vitro. inhibitory effect not specific hPAT1 via vivo, amount absorbed, suggesting that on occurs both vivo. Hence, could alter bioavailability drugs absorbed PAT1.