Apigenin, a novel candidate involving herb-drug interaction (HDI), interacts with organic anion transporter 1 (OAT1)

2017 ◽  
Vol 69 (6) ◽  
pp. 1254-1262 ◽  
Author(s):  
Ting Wu ◽  
Haixin Li ◽  
Jiasheng Chen ◽  
Ying Cao ◽  
Weimin Fu ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Anion Transporter

Renal Organic Anion Transporter-Mediated Drug-Drug Interaction between Gemcabene and Quinapril

2009 ◽  
Vol 330 (1) ◽  
pp. 191-197 ◽  
Author(s):  
Haodan Yuan ◽  
Bo Feng ◽  
Ying Yu ◽  
Jonathan Chupka ◽  
Jenny Y. Zheng ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Anion Transporter ◽  
Drug Drug Interaction

scholarly journals Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 83
Author(s):  
Yun Ju Kang ◽  
Chul Haeng Lee ◽  
Soo-Jin Park ◽  
Hye Suk Lee ◽  
Min-Koo Choi ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Rosmarinic Acid ◽  
Renal Excretion ◽  
Organic Anion ◽  
Plasma Concentrations ◽  
Pharmacokinetic Interaction ◽  
Organic Anion Transporter ◽  
Hek293 Cells ◽  
Anion Transporter

We investigated the involvement of drug transporters in the pharmacokinetics of rosmarinic acid in rats as well as the transporter-mediated drug interaction potential of rosmarinic acid in HEK293 cells overexpressing clinically important solute carrier transporters and also in rats. Intravenously injected rosmarinic acid showed bi-exponential decay and unchanged rosmarinic acid was mainly eliminated by urinary excretion, suggesting the involvement of transporters in its renal excretion. Rosmarinic acid showed organic anion transporter (OAT)1-mediated active transport with a Km of 26.5 μM and a Vmax of 69.0 pmol/min in HEK293 cells overexpressing OAT1, and the plasma concentrations of rosmarinic acid were increased by the co-injection of probenecid because of decreased renal excretion due to OAT1 inhibition. Rosmarinic acid inhibited the transport activities of OAT1, OAT3, organic anion transporting polypeptide (OATP)1B1, and OATP1B3 with IC50 values of 60.6 μM, 1.52 μM, 74.8 μM, and 91.3 μM, respectively, and the inhibitory effect of rosmarinic acid on OAT3 transport activity caused an in vivo pharmacokinetic interaction with furosemide by inhibiting its renal excretion and by increasing its plasma concentration. In conclusion, OAT1 and OAT3 are the major transporters that may regulate the pharmacokinetic properties of rosmarinic acid and may cause herb-drug interactions with rosmarinic acid, although their clinical relevance awaits further evaluation.

A novel hydrophilic interaction chromatography assay characterization of 4-pyridoxic acid, an emergent renal organic anion transporter 1/3 transporter biomarker

Bioanalysis ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 1391-1400
Author(s):  
Justin Towner ◽  
Brian Rago ◽  
David Rodrigues ◽  
Manoli Vourvahis ◽  
Chris Holliman
Keyword(s):  
Drug Interaction ◽  
Clinical Studies ◽  
Organic Anion ◽  
Plasma Concentrations ◽  
Hydrophilic Interaction Chromatography ◽  
Organic Anion Transporter ◽  
Hydrophilic Interaction ◽  
Anion Transporter ◽  
Clinical Drug

Aim: 4-pyridoxic acid (PDA) has been proposed as an endogenous biomarker for renal organic anion transporter 1/3 (OAT1/3) inhibition. Clinical data are needed to support the proposal. Materials & methods: A hydrophilic interaction chromatography (HILIC)–LC/MS/MS assay was developed and characterized to support clinical drug–drug interaction (DDI) studies. Results: A HILIC–LC/MS/MS assay was successfully developed. PDA was measured in two clinical DDI studies; one where no significant OAT1/3 inhibition was observed and a second where a known inhibitor of the transporter was dosed. In both clinical studies, PDA plasma concentrations correlate to OAT1/3 function. Conclusion: The analysis of study samples from two clinical DDI studies using a HILIC–LC/MS/MS assay contributes further evidence that PDA is an endogenous biomarker for OAT1/3 inhibition.

scholarly journals Interaction of Anticancer Drugs with Human Organic Anion Transporter hOAT4

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Chenchang Liu ◽  
Jinghui Zhang ◽  
Guofeng You
Keyword(s):  
Drug Interaction ◽  
Anticancer Drugs ◽  
Organic Anion ◽  
Inhibitory Effect ◽  
Organic Anion Transporter ◽  
Estrone Sulfate ◽  
Anion Transporters ◽  
Anion Transporter ◽  
Drug Drug Interaction ◽  
The Individual

Human organic anion transporter 4 (hOAT4) belongs to a family of multispecific organic anion transporters that play critical roles in the disposition of numerous drugs and therefore are the major sites for drug-drug interaction. Drug-drug interactions contribute significantly to the individual variation in drug response. hOAT4 is expressed in the kidney and placenta. In the current study, we examined the interaction of 36 anticancer drugs with hOAT4 in kidney COS-7 cells and placenta BeWo cells. Among the drugs tested, only epirubicin hydrochloride and dabrafenib mesylate exhibited > 50% cis-inhibitory effect, in COS-7 cells, on hOAT4-mediated uptake of estrone sulfate, a prototypical substrate for the transporter. The IC50values for epirubicin hydrochloride and dabrafenib mesylate were 5.24±0.95μM and 8.30±3.30μM, respectively. Dixon plot analysis revealed that inhibition by epirubicin hydrochloride was noncompetitive with aKi= 3μM whereas inhibition by dabrafenib mesylate was competitive with aKi= 4.26μM. Our results established that epirubicin hydrochloride and dabrafenib mesylate are inhibitors of hOAT4. Furthermore, by comparing our data with clinically relevant exposures of these drugs, we conclude that although the tendency for dabrafenib mesylate to cause drug-drug interaction through hOAT4 is insignificant in the kidney, the propensity for epirubicin hydrochloride to cause drug-drug interaction is high.

scholarly journals Drug interaction between celecoxib and methotrexate in organic anion transporter 3–transfected renal cells and in rats in vivo

2010 ◽  
Vol 640 (1-3) ◽  
pp. 168-171 ◽  
Author(s):  
Akimitsu Maeda ◽  
Shuichi Tsuruoka ◽  
Kentarou Ushijima ◽  
Yoshikatsu Kanai ◽  
Hitoshi Endou ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Renal Cells ◽  
Anion Transporter ◽  
Organic Anion Transporter 3
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