Multiple organic cation transporters contribute to the renal transport of sulpiride

Abstract Sulpiride, a selective dopamine D2 receptor blocker, is widely used for treatment of schizophrenia, depression, and gastric/duodenal ulcers. Because of the great majority of sulpiride in positive charged at physiological pH7.4, and ~70% of dose recovered in urine in unchanged form after human intravenous administration of sulpiride, we believe transporters play an important role in renal excretion of sulpiride. The aim of the present study was to explore which transporters contribute to the renal disposition of sulpiride. Our results demonstrated sulpiride was a substrate of human carnitine/organic cation transporter 1 (hOCTN1) and 2 (hOCTN2), human organic cation transporter 2 (hOCT2), human multidrug and toxin efflux extrusion protein 1 (hMATE1) and 2‐K (hMATE2‐K). Sulpiride accumulation from basolateral (BL) to apical (AP) side in MDCK‐hOCT2/pcDNA3.1 cell monolayers was much greater than that in MDCK‐hOCT2/hMATE1 cells, and cimetidine dramatically reduced the intracellular accumulation of sulpiride from BL to AP. In addition, the accumulation of sulpiride in mouse primary renal tubular cells (mPRTCs) was markedly reduced by inhibitors of Oct2 and Octns. The results implied that OCTN1, OCTN2, OCT2, MATE1 and MATE2‐K probably contributed to renal transfer of sulpiride, in which OCT2 mediated the uptake of sulpiride from the bloodstream to the proximal tubular cells, while MATEs contributed to the sulpiride efflux from the proximal tubular cells to renal lu...
Source: Biopharmaceutics and Drug Disposition - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL PAPER Source Type: research