OBJECTIVE The ABCB1 gene encodes P-glycoprotein, which limits brain concentrations of certain antidepressants. ABCB1 variation has been associated with antidepressant efficacy and side effects in small-sample studies. Cognitive impairment in major depressive disorder predicts poor treatment outcome, but ABCB1 genetic effects in patients with cognitive impairment are untested. The authors examin...

It is established that efflux transporters of the ATP-binding cassette (ABC) superfamily can affect the pharmacokinetics of drugs through mechanisms pertaining to drug absorption, elimination, and distribution. To characterize the role of multiple transporters in topotecan's pharmacokinetics, total (lactone+carboxylate) and lactone forms were measured by liquid chromatography/tandem mass spectr...

The ATP-binding cassette transporter ABCB4 is a phosphatidylcholine translocator specifically expressed at the bile canalicular membrane in hepatocytes, highly homologous to the multidrug transporter ABCB1. Variations in the ABCB4 gene sequence cause progressive familial intrahepatic cholestasis type 3. We have shown previously that the I541F mutation, when reproduced either in ABCB1 or in ABCB...

It is established that efflux transporters of the ATP-binding cassette (ABC) superfamily can affect the pharmacokinetics of drugs throughmechanisms pertaining to drug absorption, elimination, and distribution. To characterize the role of multiple transporters in topotecan’s pharmacokinetics, total (lactoneþcarboxylate) and lactone forms were measured by liquid chromatography/tandem mass spectro...

Membrane transporters and channels (collectively the transportome) govern cellular influx and efflux of ions, nutrients, and drugs. We used oligonucleotide arrays to analyze gene expression of the transportome in 60 human cancer cell lines used by the National Cancer Institute for drug screening. Correlating gene expression with the potencies of 119 standard anticancer drugs identified known dr...

T2Rs (bitter taste-sensing type 2 receptors) are expressed in the oral cavity to prevent ingestion of dietary toxins through taste avoidance. They are also expressed in other cell types, including gut enteroendocrine cells, where their physiological role is enigmatic. Previously, we proposed that T2R-dependent CCK (cholecystokinin) secretion from enteroendocrine cells limits absorption of dieta...

We conducted a case-control study to investigate the role of ABCB1 C3435T and G2677T/A in the susceptibility and prognosis of colorectal cancer patients. A total of 316 patients with colorectal cancer and 316 controls were collected between January 2009 and January 2011. Genotyping of ABCB1 C3435T and G2677T/A was conducted by the methods of Polymerase chain reaction restriction fragment length...

The second-generation tyrosine kinase inhibitor and anticancer drug axitinib is a potent, orally active inhibitor of the vascular endothelial growth factor receptors 1, 2, and 3. Axitinib has clinical activity against solid tumors such as metastatic renal cell carcinoma and advanced pancreatic cancer. We studied axitinib transport using Madin-Darby canine kidney II cells overexpressing human AB...

Organic anion-transporting polypeptides (OATPs) are important uptake transporters that can have a profound impact on the systemic pharmacokinetics, tissue distribution, and elimination of several drugs. Previous in vivo studies of the pharmacokinetics of the lipophilic camptothecin (CPT) analog gimatecan suggested that the ATP-binding cassette (ABC) B1 (P-glycoprotein) and/or ABCG2 (breast canc...

The second-generation tyrosine kinase inhibitor and anticancer drug axitinib is a potent, orally active inhibitor of the vascular endothelial growth factor receptors 1, 2, and 3. Axitinib has clinical activity against solid tumors such as metastatic renal cell carcinoma and advanced pancreatic cancer. We studied axitinib transport using Madin-Darby canine kidney II cells overexpressing human AB...