the activity of cytochrome p450 isozyme 3a4 (cyp3a4) enzyme and p-glycoprotein (p-gp) is modulated by grapefruit juice and herbal drugs. cyp3a4 is the major phase i drug metabolizing enzyme and p-gp is an atp-dependent drug efflux pump that regulates the intestinal absorption of orally administered drugs. honey is commonly consumed as a dietary supplement. however, its influence on human cyp3a4...

P-glycoprotein (P-gp), an efflux membrane transporter, is widely distributed throughout the body and is responsible for limiting cellular uptake and the distribution of xenobiotics and toxic substances. Hundreds of structurally diverse therapeutic agents are substrates to it and it impedes the absorption, permeability, and retention of the drugs, extruding them out of the cells. It is overexpre...

P-glycoprotein is a 170-kd glycosylated transmembrane protein, expressed in a variety of human cells and belonging to the adenosine triphosphate-binding cassette transporter family, whose membrane expression is functionally associated with the multidrug resistance phenotype. However, the mechanisms underlying the regulation of P-glycoprotein functions remain unclear. On the basis of some eviden...

Most antigenic peptides presented to CD8+ T cells are generated from cytosolic precursors and are translocated by TAP into the endoplasmic reticulum, where they associate with MHC class I molecules. TAP-deficient cells exhibit a limited capacity to deliver peptides from cytosolic proteins to class I molecules. One candidate for an alternative peptide transporter is P-glycoprotein, which transpo...

Huge amounts of small compound bioactivity data have been entering the public domain as a consequence of open innovation initiatives. It is now the time to carefully analyse existing bioassay data and give it a systematic structure. Our study aims to annotate prominent in vitro assays used for the determination of bioactivities of human P-glycoprotein inhibitors and substrates as they are repre...

INTRODUCTION: Studies using MDCKII and LLC-PK1 cells transfected with MDR1 cDNA indicate that ciprofloxacin is not a substrate of P-glycoprotein. However, our data has shown that transport studies done using different P-gp overexpressing cell lines (MDCKI-MDR1, MDCKII-MDR1 and L-MDR1), could lead to contradictory conclusion on whether a compound is a substrate of P-gp. The aim of our study was ...

Drug discovery and development is a complex and time consuming process which requires multidisciplinary expertise (Pracha-yasittikul et al., 2015a). It is true that bioac-tive compounds will become useless if their pharmacokinetic properties are not adequate. Pharmacokinetic properties include absorption (A), distribution (D), metabolism (M), excretion (E) and toxicity (T), or ADMET. ADMET prop...

We read with interest the paper by Wu et al. (1) purporting to show that blockade of P-glycoprotein with verapamil or itraconazole increased brain concentrations of amphotericin B (AMB). Because virtually all P-glycoprotein blockers also block other transporters, we chose to compare P-glycoprotein knockout (KO) mice (Mdr1a/1b) with isogenic FVB wild-type mice. After administration of intravenou...

P-glycoprotein has a widespread expression on normal tissues. The protein has also been strongly associated with the multidrug resistance phenotype (MDR) on tumor cells. The employment of flow cytometry and confocal microscopy has contributed to the discovery and application of new particular fluorescent dyes. Nevertheless, several studies are being performed in different cellular types neglect...