scholarly journals Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs): Influence of Protein Expression on Drug–Drug Interactions

2012 ◽  
Vol 55 (10) ◽  
pp. 4740-4763 ◽  
Author(s):  
Maria Karlgren ◽  
Anna Vildhede ◽  
Ulf Norinder ◽  
Jacek R. Wisniewski ◽  
Emi Kimoto ◽  
...  
Keyword(s):  
Protein Expression ◽  
Drug Interactions ◽  
Organic Anion ◽  
Organic Anion Transporting Polypeptides

Hepatic organic anion transporting polypeptides mediate disposition of milk thistle flavonolignans and pharmacokinetic silymarin‐drug interactions

2021 ◽  
Author(s):  
Katherine D. Lynch ◽  
Michelle L. Montonye ◽  
Dan‐Dan Tian ◽  
Tarana Arman ◽  
Victoria O. Oyanna ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Organic Anion ◽  
Milk Thistle ◽  
Organic Anion Transporting Polypeptides

scholarly journals Intestinal Ischemia-Reperfusion Suppresses Biliary Excretion of Hepatic Organic Anion Transporting Polypeptides Substrate

2013 ◽  
Vol 16 (5) ◽  
pp. 722 ◽  
Author(s):  
Hajime Maruyama ◽  
Jiro Ogura ◽  
Asuka Fujikawa ◽  
Yusuke Terada ◽  
Takashi Tsujimoto ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Protein Expression ◽  
Biliary Excretion ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Organic Anion ◽  
Mrna Levels ◽  
Organic Anion Transporting Polypeptides ◽  
Expression Levels ◽  
Intestinal Ischemia Reperfusion

Purpose. Intestinal ischemia-reperfusion (I/R) causes gut dysfunction and promotes multi-organ failure. The liver and kidney can be affected by multi-organ failure after intestinal I/R. Organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) are recognized in a broad spectrum from endogenous compounds to xenobiotics, including clinically important drugs. Therefore, it is important for understanding the pharmacokinetics to obtain evidence of alterations in OATPs and OATs expression and transport activities. In the present study, we investigated the expression of rat Oatps and Oats after intestinal I/R. Methods. We used intestinal ischemia-reperfusion (I/R) model rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Plasma concentration and biliary excretion of sulfobromophthalein (BSP), which is used as a model compound of organic anion drugs, were measured after intravenous administration in intestinal I/R rats. Results. Although Oat1 and Oat3 mRNA levels were not altered in the kidney, Oatp1a1, Oatp1b2 and Oatp2b1 mRNA levels in the liver were significantly decreased at 1-6 h after intestinal I/R. Moreover, Oatp1a1 and Oatp2b1 protein expression levels were decreased at 1 h after intestinal I/R. Plasma concentration of BSP, which is a typical substrate of Oatps, in intestinal I/R rats reperfused 1 h was increased than that in sham-operated rats. Moreover, the area under the concentration-time curve (AUC0-90) in intestinal I/R rats reperfused 1 h was significantly increased than that in sham-operated rats. The total clearance (CLtot) and the biliary clearance (CLbile) in intestinal I/R rats reperfused 1 h were significantly decreased than those in sham-operated rats. Conclusions. Oatp1a1 and Oatp2b1 expression levels are decreased by intestinal I/R. The decreases in these transporters cause alteration of pharmacokinetics of organic anion compound. The newly found influence of intestinal I/R on the expression and function of Oatps may be a key to perform appropriate drug therapy.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page

EVALUATION OF DRUG-DRUG INTERACTION IN THE HEPATOBILIARY AND RENAL TRANSPORT OF DRUGS

2005 ◽  
Vol 45 (1) ◽  
pp. 689-723 ◽  
Author(s):  
Yoshihisa Shitara ◽  
Hitoshi Sato ◽  
Yuichi Sugiyama
Keyword(s):  
Drug Interactions ◽  
Organic Anion ◽  
Renal Transport ◽  
Drug Metabolizing Enzymes ◽  
Organic Anion Transporters ◽  
Organic Anion Transporting Polypeptides ◽  
Metabolizing Enzymes ◽  
Anion Transporters ◽  
Degree Of Overlap

Recent studies have revealed the import role played by transporters in the renal and hepatobiliary excretion of many drugs. These transporters exhibit a broad substrate specificity with a degree of overlap, suggesting the possibility of transporter-mediated drug-drug interactions with other substrates. This review is an overview of the roles of transporters and the possibility of transporter-mediated drug-drug interactions. Among the large number of transporters, we compare the Ki values of inhibitors for organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) and their therapeutic unbound concentrations. Among them, cephalosporins and probenecid have the potential to produce clinically relevant OAT-mediated drug-drug interactions, whereas cyclosporin A and rifampicin may trigger OATP-mediated ones. These drugs have been reported to cause drug-drug interactions in vivo with OATs or OATP substrates, suggesting the possibility of transporter-mediated drug-drug interactions. To avoid adverse consequences of such transporter-mediated drug-drug interactions, we need to be more aware of the role played by drug transporters as well as those caused by drug metabolizing enzymes.

scholarly journals Induction of Human Intestinal and Hepatic Organic Anion Transporting Polypeptides: Where Is the Evidence for Its Relevance in Drug-Drug Interactions?

2019 ◽  
Vol 48 (3) ◽  
pp. 205-216 ◽  
Author(s):  
A. David Rodrigues ◽  
Yurong Lai ◽  
Hong Shen ◽  
Manthena V.S. Varma ◽  
Andrew Rowland ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Organic Anion ◽  
Organic Anion Transporting Polypeptides

scholarly journals Post-translational regulation of the major drug transporters in the families of organic anion transporters and organic anion–transporting polypeptides

2020 ◽  
Vol 295 (50) ◽  
pp. 17349-17364
Author(s):  
Wooin Lee ◽  
Jeong-min Ha ◽  
Yuichi Sugiyama
Keyword(s):  
Drug Therapy ◽  
Drug Interactions ◽  
Drug Exposure ◽  
Organic Anion ◽  
Transcriptional Level ◽  
Organic Anion Transporters ◽  
Post Translational Modification ◽  
Organic Anion Transporting Polypeptides ◽  
Related Factors ◽  
Anion Transporters

The organic anion transporters (OATs) and organic anion–transporting polypeptides (OATPs) belong to the solute carrier (SLC) transporter superfamily and play important roles in handling various endogenous and exogenous compounds of anionic charge. The OATs and OATPs are often implicated in drug therapy by impacting the pharmacokinetics of clinically important drugs and, thereby, drug exposure in the target organs or cells. Various mechanisms (e.g. genetic, environmental, and disease-related factors, drug-drug interactions, and food-drug interactions) can lead to variations in the expression and activity of the anion drug-transporting proteins of OATs and OATPs, possibly impacting the therapeutic outcomes. Previous investigations mainly focused on the regulation at the transcriptional level and drug-drug interactions as competing substrates or inhibitors. Recently, evidence has accumulated that cellular trafficking, post-translational modification, and degradation mechanisms serve as another important layer for the mechanisms underlying the variations in the OATs and OATPs. This review will provide a brief overview of the major OATs and OATPs implicated in drug therapy and summarize recent progress in our understanding of the post-translational modifications, in particular ubiquitination and degradation pathways of the individual OATs and OATPs implicated in drug therapy.

Sign in / Sign up

Export Citation Format

Share Document