P-glycoprotein (P-gp), one of the important drug-efflux pumps, is known to affect pharmacokinetics and pharmacodynamics of P-gp substrate drugs. We have previously reported that intestinal P-gp expression levels are transiently decreased in streptozotocin (STZ)-induced type 1 diabetic mouse model. Herein, we examined the analgesic effects of orally administered morphine and its pharmacokinetic ...

BACKGROUND The use of upstream small-molecule glycoprotein (GP) IIb/IIIa inhibitors in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been studied in multiple randomized clinical trials. We systematically reviewed the effect of upstream GP IIb/IIIa inhibitor use in NSTE ACS as reported in published clinical trials. METHODS AND RESULTS Randomized clinical trials of upstream s...

factor receptor mutant vIII; Mdr1, gene encoding the murine p-glycoprotein; MDR1, gene encoding the human p-glycoprotein; Bcrp1, gene encoding the murine breast cancer resistance protein. This article has not been copyedited and formatted. The final version may differ from this version. Abstract Gefitinib is an orally active inhibitor of the epidermal growth factor receptor (EGFR) approved for ...

Small molecule inhibitors targeting the mitogen-activated protein kinase pathway (Braf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase) have had success in extending survival for patients with metastatic melanoma. Unfortunately, resistance may occur via cross-activation of alternate signaling pathways. One approach to overcome resistance is to simultaneously target...

Overexpression of P-glycoprotein (P-gp) in the brain is an important mechanism involved in drug‑resistant epilepsy (DRE). High-mobility group box 1 (HMGB1), an inflammatory cytokine, significantly increases following seizures and may be involved in upregulation of P‑gp. However, the underlying mechanisms remain elusive. The aim of the present study was to evaluate the role of HMGB1 and its down...

Multidrug resistance (MDR) is a major clinical obstacle in the treatment of several cancers including hematological malignancies and solid tumors. The ATP-binding cassette transporter B1 (ABCB1) gene and its product, P-glycoprotein (P-gp), is one molecule that is involved in drug resistance. Here we report on the effect of decitabine (5-aza-2'-deoxycytidine), an inhibitor of DNA methyltransfera...

P-glycoprotein (P-gp) is an ATP-dependent transporter localized at the apical membrane of the kidney proximal tubules, which plays a role in the efflux of cationic and amphipathic endogenous waste products and xenobiotics, such as drugs, into urine. Studies in mice deficient in P-gp showed generalized proximal tubular dysfunction similar to the phenotype of patients with cystinosis, an autosoma...

This study aimed to investigate the in vivo relevance of P-glycoprotein (P-gp) in the pharmacokinetics and adverse effect of phenformin. To investigate the involvement of P-gp in the transport of phenformin, a bi-directional transport of phenformin was carried out in LLC-PK1 cells overexpressing P-gp, LLC-PK1-Pgp. Basal to apical transport of phenformin was 3.9-fold greater than apical to basal...

The effect of macelignan, a phytoestrogen, on P-gp function was investigated using multidrug resistant cancer cells overexpressing P-gp (NCI/ADR-RES) and the fluorescent P-gp substrates, daunorubicin and rhodamine 123. Macelignan (40 microM) increased the cellular accumulation of daunorubicin by approximately threefold in NCI/ADR-RES cells, whereas it did not alter the cellular accumulation of ...

A small library of bivalent agents was designed to probe the substrate binding sites of the human multidrug transporter P-glycoprotein (P-gp). The bivalent agents were composed of two copies of the P-gp substrate emetine, linked by tethers of varied composition. An optimum distance between the emetine molecules of approximately 10 A was found to be necessary for blocking transport of the known ...