Characterization of cytochrome P450 (CYP) 2D6 drugs as substrates of human organic cation transporters and multidrug and toxin extrusion proteins

Interactions of tyrosine kinase inhibitors with organic cation transporters and multidrug and toxic compound extrusion proteins.

The drug-drug interaction (DDI) potential of tyrosine kinase inhibitors (TKI) as interacting drugs via transporter inhibition has not been fully assessed. Here, we estimated the half maximal inhibitory concentration (IC(50)) values for 8 small-molecule TKIs (imatinib, dasatinib, nilotinib, gefitinib, erlotinib, sunitinib, lapatinib, and sorafenib) on [(14)C]metformin transport by human organic ...

Transport of paraquat by human organic cation transporters and multidrug and toxic compound extrusion family.

Paraquat (N,N-dimethyl-4-4'-bipiridinium; PQ), a widely used herbicide, when ingested accidentally or intentionally can cause major organ toxicities in lung, liver, and kidney. Because PQ is primarily eliminated in the kidney, renal elimination, including tubular transport, plays a critical role in controlling systemic exposure to the herbicide. The goal of this study was to determine the molec...

Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family).

We have examined the role of the human organic cation transporters [hOCTs and human novel organic cation transporter (hOCTN); SLC22A1-5] and apical multidrug and toxin extrusion (hMATE) in the cellular accumulation and cytotoxicity of platinum agents using the human embryonic kidney (HEK) 293 cells transiently transfected with the transporter cDNAs. Both the cytotoxicity and accumulation of cis...

Interaction and Transport of Methamphetamine and its Primary Metabolites by Organic Cation and Multidrug and Toxin Extrusion Transporters.

Methamphetamine is one of the most abused illicit drugs with roughly 1.2 million users in the United States alone. A large portion of methamphetamine and its metabolites is eliminated by the kidney with renal clearance larger than glomerular filtration clearance. Yet the mechanism of active renal secretion is poorly understood. The goals of this study were to characterize the interaction of met...

Atenolol Renal Secretion Is Mediated by Human Organic Cation Transporter 2 (hOCT2) and Multidrug and Toxin Extrusion Proteins (hMATEs)