Advertisement

Topics

Organic anion transporter 3 (OAT3)-mediated transport of dicaffeoylquinic acids and prediction of potential drug-drug interaction.

08:00 EDT 27th March 2019 | BioPortfolio

Summary of "Organic anion transporter 3 (OAT3)-mediated transport of dicaffeoylquinic acids and prediction of potential drug-drug interaction."

Dicaffeoylquinic acids (DCQAs) are widely distributed in daily food and herb medicine (such as Dengzhanxiyin injection) with multiple health benefits and pharmacological activities. However, drug-drug Interactions (DDIs) between DCQAs and possible concomitant drugs were not fully understood in clinic. The purpose of present study was to investigate the role of organic anion transporters (OATs) in the transport of DCQAs and to explore the potential clinical DDIs using in vitro transporter assays. Uptake study using hOAT1/hOAT3-transfected HEK293 cells revealed that none of DCQAs was OAT1 substrate, while 3,4-DCQA, 3,5-DCQA, and 4,5-DCQA were substrates of OAT3 with Km values of 119.7 ± 28.8, 269.3 ± 129.5 and 53.2 ± 32.1 μM, respectively. The docking analysis revealed that 3,4-DCQA, 3,5-DCQA, and 4,5-DCQA were effectively embedded in the active site of OAT3 and fitted well with the cavity in three-dimensional space. Moreover, the classical substrates/inhibitors of OAT decreased the accumulation of 3,4-DCQA, 3,5-DCQA, and 4,5-DCQA in kidney slices, suggesting potential DDI risks with co-administration of substrate drugs of OAT. In fact, antivirals, antibiotics, neuroprotective agents, and PPIs (proton pump inhibitors) all showed varying degrees of inhibition of OAT3-mediated uptake of 3,4-DCQA, 3,5-DCQA, and 4,5-DCQA in vitro. For cefaclor, ceftizoxime, pantoprazole, and zidovudine, in particular, their IC values were <10 times the maximal free plasma concentration, indicating potential clinically relevant DDIs when used together with DCQAs. These findings provided useful information for the prediction of DDIs between DCQAs and OAT3 inhibitors, and rational application of herbal medicines containing DCQAs in clinic.

Affiliation

Journal Details

This article was published in the following journal.

Name: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720
Pages:

Links

DeepDyve research library

PubMed Articles [15197 Associated PubMed Articles listed on BioPortfolio]

Isoflavones from Camphorosma lessingii Inhibit the Organic Anion Transporters OAT1 and OAT3.

Phytochemical investigation of has resulted in the isolation of four previously unreported isoflavones (1: -4: ) and eight known compounds (5: -12: ). Nine of these compounds (1: -6, 8: -10: ) are re...

Organic anion transporter 1 and 3 influence cellular energy metabolism in renal proximal tubule cells.

Organic anion transporter (OAT) 1 and 3 are, besides uptake transporters, key in several cellular metabolic pathways. The underlying mechanisms are largely unknown. Hence, we used human conditionally ...

Dihydrophenanthrenes from Juncus effusus as Inhibitors of OAT1 and OAT3.

Organic anion transporters 1 (OAT1) and 3 (OAT3) play important roles in the renal elimination of a range of substrate molecules. Little is known about natural products that can modulate OAT1 and OAT3...

The Mechanistic Links between Insulin and Human Organic Anion Transporter 4.

Human organic anion transporter 4 (hOAT4) belongs to a class of organic anion transporters that exert critical function in the secretion, absorption, and distribution of numerous drugs in the body, su...

Increased expression of renal drug transporters in a mouse model of familial Alzheimer's disease.

It is well established that the expression and function of drug transporters at the blood-brain barrier (BBB) are altered in Alzheimer's disease (AD). However, we recently demonstrated in a mouse mode...

Clinical Trials [2246 Associated Clinical Trials listed on BioPortfolio]

Effect of Genetic Variation in the Transporter, OAT3, on the Renal Secretion of Cefotaxime

In the proposed study, we plan to use a genotype to phenotype strategy to study the role of the organic anion transporter, OAT3, in drug response. More specifically we will examine the co...

A Study to Investigate the Potential Influence of Nitisinone on the Metabolism and the Transport of Other Drugs in Healthy Volunteers

An open-label, non-randomized, 2-arm, 2-period fixed sequence phase 1 study to evaluate the potential inhibition of nitisinone on cytochrome P450 2C9, 2D6, and 2E1 and the organic anion tr...

Genetic Variation in Organic Cation Transport 1 (OCT1) and Its Significance for Morphine Pharmacokinetics

The main objective of the trial is to investigate the effect of known genetic variants in organic cation transporter 1 (OCT1) on the effect of morphine after major surgery

Impact of Polymorphisms of OAT1, OAT3, and OCT2 on Transportation of Potential Nephrotoxic Drugs

Transporters in kidney are critical in detoxification and elimination of xenobiotics from systemic circulation, and thus are major determinants of drug response and sensitivity. Transporte...

Drug Transporter Interaction Study PHENTRA_2015_KPUK

The objective of the present study is to contribute to establishing in vivo phenotyping procedures for organic anionic transporter polypeptide 1B1 (OATP1B1), organic cation transporters 1 ...

Medical and Biotech [MESH] Definitions

A sodium-independent organic anion transporter that functions in the uptake of various drugs and endogenous compounds including ESTRADIOL; TAUROCHOLATE; LEUKOTRIENE C4; and METHOTREXATE. It also functions in clearing BILE ACIDS and organic anions from the liver. Mutations in the SLCO1B3 gene are associated with Rotor Type HYPERBILIRUBINEMIA.

An organic anion transporter found in human liver. It is capable of transporting a variety organic anions and mediates sodium-independent uptake of bile in the liver.

An organic anion transporter found in human liver. It is capable of transporting a variety organic anions and mediates sodium-independent uptake of bile in the liver.

A subclass of ORGANIC ANION TRANSPORTERS whose transport of organic anions is linked directly to the hydrolysis of ATP. The subclass includes those ATP-BINDING CASSETTE TRANSPORTERS that transport organic ions.

A subclass of ORGANIC ANION TRANSPORTERS whose transport of organic anions is driven either directly or indirectly by a gradient of sodium ions.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Pharmacy
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Food
Food is any substance consumed to provide nutritional support for the body. It is usually of plant or animal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals. The substance is ingested by an organism ...


Searches Linking to this Article