Studies were designed to quantitatively assess the mRNA expression of 1) 10 cytochrome P450 (P450) enzymes in human cornea, iris-ciliary body (ICB), and retina/choroid relative to their levels in the liver, and of 2) 21 drug transporters in these tissues relative to their levels in human small intestine, liver, or kidney. Potential species differences in mRNA expression of PEPT1, PEPT2, and MDR...

Recently, Ribosome-Inactivating Proteins (RIPs) as a class of anticancer medicines have garnered considerable attention due to their novel mechanism. Although the medications are small, RIPs utilize Large-Size Effect (LSE) block efflux procedure that regulated through Drug Resistance Transporters (DRTs), and protect host cells from drug transfection. There many significant challenges for therap...

Drug resistance (DR) is the major limiting factor in the successful treatment of systemic neoplasia with cytotoxic chemotherapy. DR can be either intrinsic or acquired, and although the development and clinical implications are different, the underlying mechanisms are likely to be similar. Most causes for DR are pharmacodynamic in nature, result from adaptations within the tumor cell and includ...

The blood-testis barrier (BTB) provides an efficient barrier to restrict paracellular and transcellular transport of substances, such as toxicants and drugs, limiting their entry to the testis to cause injury. This is achieved by the coordinated actions of efflux and influx transporters at the BTB, which are integral membrane proteins that interact with their substrates, such as drugs and toxic...

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...

We examined the roles of diffusion, convection and capillary transporters in solute removal from extracellular space (ECS) of the brain. Radiolabeled solutes (eight with passive distribution and four with capillary or cell transporters) were injected into the brains of rats (n=497) and multiple-time point experiments measured the amount remaining in brain as a function of time. For passively di...

There is an increasing appreciation of the role that transport proteins play in the absorption, distribution, and elimination of a wide variety of drugs in clinical use. These transporters can be divided into efflux transporters belonging to the ATP-binding cassette (ABC) family and solute carrier (SLC) family members that mediate the influx or bidirectional movement of drugs across the cell me...

Numerous studies in the past 25 years have shown that most compounds, generated in metabolic processes (metabolic intermediates and products; endogenous compounds) or introduced orally or parenterally (nutritive compounds, medicaments, environmental toxins and other xenobiotics), do not enter or exit cells freely, by simple diffusion. Rather, their transmembrane movement is mediated by various ...

Knowledge of free drug intracellular concentration is necessary to predict the impacts of drugs on intracellular targets. The goal of this study was to develop models to predict free intracellular drug concentrations in the presence of apical efflux transporters. The apical efflux transporter P-glycoprotein (P-gp), encoded by human gene multidrug resistance 1 (MDR1), was studied. Apparent perme...