This study investigated the influence of genetic polymorphisms of metformin transporters on long-term glycemic control and lipid status in type 2 diabetes patients in the everyday clinical setting. In total 135 patients treated with combination of metformin and sulphonylurea for at least 6 months were genotyped for SLC22A1 rs628031 and SLC47A1 rs2289669 polymorphisms. Relatively good blood gluc...

The renal tubular secretion of cationic drugs is dominated by basolateral organic cation transporter 2 (rOCT2/SLC22A2) and luminal multidrug and toxin extrusion 1 (rMATE1/SLC47A1). Little is known about the variation in the expression of these renal transporters after liver ischemia-reperfusion (I/R) injury. Here, we examined the pharmacokinetics of a cationic drug, cimetidine, and renal rOCT2 ...

Multidrug and toxin extrusion 1 (MATE1/SLC47A1) is expressed in the brush-border membrane of renal proximal tubules and mediates the efflux of cationic drugs. In the present study, the role of MATE1 in the nephrotoxicity of cisplatin was investigated in vivo and in vitro. Cisplatin (15mg/kg) was administered intraperitoneally to wild-type (Mate1(+/+)) and Mate1 knockout (Mate1(-/-)) mice. Lifes...

Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for gene-metformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates ...

Type 2 diabetes mellitus (T2DM) is a worldwide epidemic with considerable health and economic consequences. T2DM patients are often treated with more than one drug, including oral antidiabetic drugs (OAD) and drugs used to treat diabetic complications, such as dyslipidemia and hypertension. If genetic testing could be employed to predict treatment outcome, appropriate measures could be taken to...

Metformin is a common co-medication for many diseases and the victim of clinical drug-drug interactions (DDIs) perpetrated by cimetidine, trimethoprim and pyrimethamine, resulting in decreased active renal clearance due to inhibition of organic cation transport proteins and increased plasma exposure of metformin. To understand whether area under the plasma concentration-time curve (AUC) increas...

Many drugs are largely hydrophobic molecules; a transporter might conceivably insert these into the plasma membrane. At least 18 transporters from diverse families have been reported to transport model compound estrone sulfate alias estrone-3-sulfate (E3S). Out of these, we recently examined SLC22A11 (OAT4). We concluded comparison E3S and uric acid that does not translocate cytosol, but Here p...

Background and Purpose The metabolic activity of cytochrome P450 (CYP) 2D6 is highly variable CYP2D6 genotypes insufficiently explain the extensive intermediate phenotypes, limiting prediction drug response plus adverse reactions. Since prototypic substrates are positively charged, aim this study was to evaluate organic cation transporters (OCTs) multidrug toxin extrusion proteins (MATEs) as po...

Multidrug and toxin extrusion 1 (MATE1/SLC47A1) is important for excretion of organic cations in the kidney and liver, where it is located on the luminal side. Although its functional and regulatory characteristics have been clarified, its pharmacokinetic roles in vivo have yet to be elucidated. In the present study, to clarify the relevance of MATE1 in vivo, targeted disruption of the murine M...

Cimetidine, an H₂ receptor antagonist, has been used to investigate the tubular secretion of organic cations in human kidney. We report a systematic comprehensive analysis of the inhibition potency of cimetidine for the influx and efflux transporters of organic cations [human organic cation transporter 1 (hOCT1) and hOCT2 and human multidrug and toxin extrusion 1 (hMATE1) and hMATE2-K, respecti...