Sorafenib is a second-generation, orally active multikinase inhibitor that is approved for the treatment of patients with advanced renal cell carcinoma and patients with unresectable hepatocellular carcinoma. We studied active transport of sorafenib in MDCK-II cells expressing human P-glycoprotein (P-gp/ABCB1) or ABCG2 (breast cancer resistance protein) or murine Abcg2. Sorafenib was moderately...

T restoration of coronary flow after an acute myocardial infarction (AMI) has been the most remarkable advance in the treatment of acute coronary syndromes in recent decades. Pharmacological and mechanical ways of achieving rapid and complete reperfusion of epicardial arteries have been the goal of many clinical trials. Questions such as whether PCI is superior to fibrinolysis, or if bolus lyti...

5,7-Dimethoxyfl avone (5,7-DMF) is a natural polymethoxyfl avone, and acts as an inhibitor of ABC efflux transporters (BCRP, MRP2 and/ or P-gp), rosuvastatin taken up via OATP2B1 secreted by BCRP MRP2. In this study, we investigated the effect 5,7-DMF on transport through apical membrane accumulation in Caco-2 cells. Furthermore, whether mediated monocarboxylate transporter 1 (MCT1), addition t...

Drug resistance is a crucial obstacle to achieve satisfactory chemotherapeutic effects. Numerous studies have shown that the PI3K/Akt signaling pathway plays significant role in various processes of cellular events and tumor progression, while few focused on drug endothelial cells. The present study aims explore relationship anticancer drugs human microvessel cells (HMEC-1). We established stab...

Effective pharmacologic treatment of pain with opioids requires that these drugs attain efficacious concentrations in the central nervous system (CNS). A primary determinant of CNS drug permeation is P-glycoprotein (P-gp), an endogenous blood-brain barrier (BBB) efflux transporter that is involved in brain-to-blood transport of opioid analgesics (i.e., morphine). Recently, the nuclear receptor ...

Apoptotic resistance is the main obstacle for treating cancer patients with chemotherapeutic drugs. Multidrug resistance (MDR) is often characterized by the expression of P-glycoprotein (P-gp), a 170-KD ATP-dependent drug efflux protein. Functional P-gp can confer resistance to activate caspase-8 and -3 dependent apoptosis induced by a range of different stimuli, including tumor necrosis and ch...

The current view of multidrug resisitance is that overexpression of membrane P-glycoprotein (P-gp) is a major causative factor. However, the controversial presence of subcellular P-gp may also participate in the drug resistance. In this study, we sought to investigate the localization and functional characterization of P-gp in mitochondria isolate...

The combination of passive drug permeability, affinity for uptake and efflux transporters as well as gastrointestinal metabolism defines net drug absorption. Efflux mechanisms are often overlooked when examining the absorption phase of drug bioavailability. Knowing the affinity of antimalarials for efflux transporters such as P-glycoprotein (P-gp) may assist in the determination of drug absorpt...

Edoxaban (the free base of DU-176b), an oral direct factor Xa inhibitor, is mainly excreted unchanged into urine and feces. Because active membrane transport processes such as active renal secretion, biliary excretion, and/or intestinal secretion, and the incomplete absorption of edoxaban after oral administration have been observed, the involvement of drug transporters in the disposition of ed...