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• W2166438523 abstract "6<i>β</i>-Hydroxycortisol (6<i>β</i>-OHF) is a substrate of the organic anion transporter 3 (OAT3) and the multidrug and toxin extrusion proteins MATE1 and MATE-2K in the corresponding cDNA-transfected cells. This study aimed to examine the contribution of OAT3 and MATEs to the urinary excretion of 6<i>β</i>-OHF in humans using the appropriate in vivo inhibitors, probenecid and pyrimethamine, for OAT3 and MATEs, respectively. Oat3(–/–) mice showed significantly reduced renal clearance of 6<i>β</i>-OHF (CL_{renal, 6}<i>_β</i>_-OHF) compared with wild-type mice (18.1 ± 1.5 versus 7.60 ± 1.8 ml/min/kg). 6<i>β</i>-OHF uptake by human kidney slices was inhibited significantly by probenecid to 20–45% of the control values and partly by 1-methyl-4-phenylpyridinium. 6<i>β</i>-OHF plasma concentration and the amount of 6<i>β</i>-OHF excreted into the urine (X₆<i>_β</i>_-OHF) were measured in healthy subjects enrolled in drug-drug interaction studies of benzylpenicillin alone or with probenecid (study 1), adefovir alone or with probenecid (study 2), and metformin alone or with pyrimethamine (study 3). Probenecid treatment caused a 57 and 76% increase in the area under the plasma concentration–time curve for 6<i>β</i>-OHF (AUC₆<i>_β</i>_-OHF) in studies 1 and 2, respectively, but did not affect X₆<i>_β</i>_-OHF. Consequently, CL_{renal, 6}<i>_β</i>_-OHF (milliliters per minute) decreased significantly from 231 ± 11 to 135 ± 9 and from 225 ± 26 to 141 ± 12 after probenecid administration in studies 1 and 2, respectively. By contrast, neither AUC₆<i>_β</i>_-OHF nor CL_{renal, 6}<i>_β</i>_-OHF was significantly altered by pyrimethamine administration. Taken together, these data suggest that OAT3 plays a significant role in the urinary excretion of 6<i>β</i>-OHF, and that 6<i>β</i>-OHF can be used to investigate the perpetrators of the pharmacokinetic drug interactions involving OAT3 in humans." @default.
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• W2166438523 date "2014-01-31" @default.
• W2166438523 modified "2023-10-17" @default.
• W2166438523 title "6<i>β</i>-Hydroxycortisol Is an Endogenous Probe for Evaluation of Drug–Drug Interactions Involving a Multispecific Renal Organic Anion Transporter, OAT3/<i>SLC22A8</i>, in Healthy Subjects" @default.
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• W2166438523 doi "https://doi.org/10.1124/dmd.113.055475" @default.
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