Transport of compound

Suction lysimeters are required for some field-scale groundwater monitoring studies to monitor the transport of compounds of interest through the unsaturated zone. Unlike monitoring wells or water supply wells that sample water from the saturated zone, suction lysimeters sample water from the unsaturated zone. This section provides a summary of the installation and sampling procedures for pressure-vacuum suction lysimeters. A detailed discussion of unsaturated zone sampling devices is available elsewhere. 

Nicklin, P., Irwin, B., Hassan, I., Williamson, I., MacKay, M., Permeable support type influence the transport of compounds across Caco-2 cells, Int. J. Pharm. 1992, 83, 197-209. 

While there are limitations associated with the use of an in vitro permeability model for assessing the transport of compounds across the buccal mucosa, it can still be useful in assessing and comparing the permeability of compounds under different conditions, such as pH, temperature, and osmolarity, which provide valuable information on the mechanisms involved in drug transport. Additionally, the preliminary effects of potential chemical penetration enhancers or formulation excipients may be assessed, and these may provide a substantial rationale for subsequently assessing the effect of these agents in man. 

MDCK Madin-Darby canine kidney (MDCK) cells have received attention as an alternative to Caco-2 cells for permeability measurements. When grown under standard culture conditions, MDCK cells develop tight junctions and form monolayers of polarized cells. The main advantage over Caco-2 cells is the shorter culture time to confluence (3-5 days). The transep-ithelial electrical resistance of MDCK cells is lower than that of Caco-2 cells and thus, closer to the TEER of the small intestine in vivo. The permeability coefficients of hydrophilic compounds are usually lower in Caco-2 cells than in MDCK cells, which is consistent with the lower TEER values for MDCK cell monolayers. The nonhuman (canine) and nonintestinal (renal) origin of MDCK cells is considered as a disadvantage. They have low expression levels of transporter proteins and low metabolic activity [34], MDCK cells that are stably transfected with P-gp/MDRl are often proposed as an alternative for Caco-2 cells to study bidirectional transport of compounds and, more... 

LLC-PK1 Cells derived from pig kidney epithelial cells (LLC-PK1) have been used as an alternative to Caco-2 cells for assessing the permeability for test compounds [153, 85], LLC-PK1 cells are more easily transfected than Caco-2 cells. Especially the LLC-PK1 line stably transfected with P-gp/MDRl has been reported as a tool to study bidirectional transport of compounds [142, 58, 180],... 

The facilitated transport of compounds by colloids, illustrated schematically in Figure 1.1, is important in several areas and especially in the study of the fate and transport processes of hydrophobic organic compounds and metal ions in the environment. This facilitated transport also has implications in other areas in which colloid diffusion through porous... 

Active transport of compounds by the tubular cells. Compounds that are actively transported from the blood into the tubular fluid may accumulate in the proximal tubular cells, especially at concentrations where saturation of the transport system occurs. Again, concentrations to which tubular cells are exposed may be very much higher than in the bloodstream. An example of this is the drug cephaloridine, which causes proximal tubular damage as discussed in more detail in chapter 7. 

Although there is a widespread perception that wild-type MDCK cells contain insignificant levels of P-gp to affect substrate transport, it has been demonstrated that this is not the case. It was shown that the transport of vinblastine sulfate across MDCK monolayers was indeed apically polarized (203). These results were duplicated by Hirst et al. using the same test compound, verapamil, in two different strains of MDCK cells. The transport profiles of verapamil showed polarity in both a high-resistance strain [TEER 2000 Q-cm2 and a low-resistance strain (TEER < 200 Q-cm2] (365). Recently, parallel studies were performed measuring the transport of a novel peptide, K02, across both MDCK and Caco-2 cells (364). The results showed nearly identical profiles for the AP to BL and BL to AP transport of this agent in both cell types. Although it is unlikely that all P-gp substrates will behave identically in both cell lines, these studies indicate that there is sufficient P-gp expression in MDCK cells to affect transport studies. Thus, MDCK cells can be used to evaluate the transport of compounds that are suspected to be substrates of P-gp. 

Some efforts have been made to determine the effect P-gp has on its substrates by use of in situ perfusion methods, including intestinal perfusion, liver perfusion, kidney perfusion, and brain perfusion. These experiments allow the researcher to study the transport of compounds in a physiologically relevant environment in which the integrity of the organ is preserved with regards to cell polarity and representation of all cell types seen in the organ. Furthermore, the reduction in complexity of in situ models versus in vivo studies facilitates the conduct of complex studies and allows more definitive conclusions to be made regarding the role P-gp may play in disposition. 

Troutman MD, Thakker DR. Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res 2003 20(8) 1210-1224. 

Nicklin P, Irwin B, Hassan I et al. (1992) Permeable support type influences the transport of compounds across CACO-2 cells. Int J Pharm 93 197-209 Pappenheimer JR, Reiss KZ (1987) Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat. J Membr Biol 100 123-136 Peters WHM, Reolofs HMJ (1992) Biochemical characterization of resistance to mitoxantrone and adriamycin in CACO-2 human colon adenocarcinoma cells a possible role for glutathione-S-transferase. Cancer Res 52 1886-1890... 

Duizer E, Stenhuis WS, Penninks AH, Groten JP (1995) Transport of compounds across monolayers of intestinal cell lines comparison of IEC-18 and CACO-2. Ital J Gastroenterol 27 154... 

There are an increasing number of proteins of interest for drug discovery that are described as mediating the transport of compounds across the cell monolayer... 

In contrast to the above-discussed molecular transport mechanisms, endocytosis, exocytosis, and transcytosis represent the transport of compounds across plasma membranes along with the bulk of their surrounding aqueous medium through vesicle formation (invagination), translocation of the vesicle, and subsequent membrane fusion, a process that also requires energy. These topics are not covered in this article. 

The separation technique can be used in two different ways for the measurements of physico-chemical parameters. In one approach the propenies of the compounds are characterised directly from the chromatographic retention which is determined by the interaction of solutes with the stationary and the mobile phases. This approach can be used for lipophilicity determination, measurements of serum albumin binding and estimating the membrane transport of compounds from their retention on immobilised artificial membrane. 

All of these features, including their regulatory systems, provide the physiological basis to understand changed BBB functionality and permeability and therefore the transport of compounds into and out of the brain. Moreover, these influx and efflux systems also maintain BBB functionality by transporting substances in and out of the endothelial compartment. Therefore, the BBB can be considered an... 

Production of Transactinoid Elements, Synthesis and Transportation of Compounds... 

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