OAT3 Mediated Interaction between Steviol Acyl Glucuronide and Probenecid: In Vitro and In Vivo Investigations

Abstract

Steviol acyl glucuronide (SVAG) is a circulating metabolite formed after the ingestion of rebaudioside A, a naturally occurring sweetner with functional activities. Our previous studies have demonstrated that transporters particularly OAT3 played an important role in renal clearance of SVAG. The present study aimed to investigate the inhibitory effect of probenecid on OAT3 mediated SVAG transport using in vitro and in vivo systems. In the hOAT3 stably transfected HEK293 cell line, probenecid exhibited a dose‐dependent inhibition of SVAG uptake, with an IC50 value of 4.95 μM. In rat kidney slices, the uptake of SVAG was markedly inhibited by probenecid (67.5%), estrone‐3‐sulfate (41.9%), and para‐aminohippurate (PAH, 27.0%), respectively. In rats given an oral dose of 15 mg/kg of rebaudioside A, the Tmax, Cmax and AUC6–8 of SVAG were 6.25 hr, 176 ng/mL and 213.8 ng/mL*hr, respectively. In contrast, an intravenous dose of probenecid (20 mg/kg) led to an increase of Cmax and AUC by 2.15 and 1.71 folds, respectively, while Tmax remained relatively unchanged. Taken together, the inhibition effect on SVAG uptake in the presence of probenecid was mediated via OAT3. As OAT3 is a major uptake transporter in the kidney, the inhibition of OAT3 activity may alter SVAG's renal clearance. It is thus prudent to investigate transporter‐mediated food‐drug interactions and ensure safe and effective use of those products.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.