Permeation, cellular

Sawada and coworkers [25-27] studied the iso-pH 7.4 MDCK permeabilities of very lipophilic molecules, including chlorpromazine (CPZ) [25], These authors included 3% wt/vol bovine serum albumin (BSA) on the apical (donor) side, and 0.1-3% BSA on the basolateral (acceptor) side, and found that plasma protein binding greatly affected the ability of molecules to permeate cellular barriers. They observed cell tissue retention of CPZ ranging from 65 to 85%, depending on the... 

Bassingthwaighte, J. B., C. Goresky, and J. Linehan. 1998. Whole Organ Approaches to Cellular Metabolism Permeation, Cellular Uptake and Product Formation, Springer, New York, NY. 

Foamed or Cellular CeUular plastics such as polyurethane and polystyrene do not hold up or perform well in the ciyogenic temperature range because of permeation of the cell strnc tnre by water vapor, which in turn increases the heat-transfer rate. CeUular glass holds up better and is less permeable. 

The simplest case of pharmacokinetics is intravenous injection [1]. In this case the drug is injected directly into the bloodstream. The drug may permeate to different tissues depending on its ability to get across the blood vessel walls and the cellular barriers in the particular tissue targets (Fig. 1). If the drug has small molecular weight and adequate... 

While in vivo studies assess absorption rates as process-lumped time constants from blood level versus time data, these rate parameters encompass the kinetics of dosage-form release, GI transit, metabolism, and membrane permeation. The use of isolated tissue and cellular preparations to screen for drug absorption potential and to evaluate absorption rate limits at the tissue and cellular levels has been expanded by the pharmaceutical industry over the past several years. For more detail in this regard, the reader is referred to an article by Stewart et al. [68] for references on these preparations and for additional details on the various experimental techniques outlined below. 

A new technique to prepare nC60 (fullerene sonication in methanol) has been used, but in this case the cluster sizes are not homogeneous. This preparation permeates the cell membrane of normal and malignant breast epithelial cells (MCF10A and MDA MB 231 or MDA MB 435, respectively) without interfering with cellular events. Also the incubation with high concentration (200ppm) does not adversely impact cell proliferation (Levi et al., 2006). 

Coumarinic acid is another phenylpropanoic acid pro-moiety used to prepare double prodrugs of amines (in analogy with the phenylpropanamides shown in Fig. 8.23), as well as cyclic prodrugs of a number of peptides (8.189) [242-246], These studies confirm the considerable potential of the cyclic prodrug strategy, such compounds being characterized by metabolic stability to peptidases and good cellular permeation. 

O. S. Gudmundsson, K. Nimkar, S. Gangwar, T. Siahaan, R. T. Borchardt, Phenylpro-pionic Acid-Based Cyclic Prodrugs of Opioid Peptides That Exhibit Metabolic Stability to Peptidases and Excellent Cellular Permeation , Pharm. Res. 1999, 16, 16-23. 

Practically all anaerobic Gram-negative bacteria are resistant to lincosamides. Resistance to lincosamides can occur because of the inability of drugs to permeate through the cellular membrane of bacteria, or because of changes in the ribosomal-binding regions. 

Achieving cell permeation may, in him, reduce the free Fe(III) pool, shifting the cellular equilibrium Fe(II)/Fe(III) toward Fe(III), thereby reducing the level of Fe(II) free to participate in the Fenton reaction (see Section III). 

Falten et al. recently reported that phospholipid membrane vesicles can be con-stmcted on a filter scaffold without any organic solvent [57-60]. In this system, the phospholipid vesicle occupies the filter pores to form a permeation barrier. This is more relevant to the cellular membrane than PAMPA membranes with organic solvent. The membrane can be stored up to two weeks without significant change and is stable at pH 2-8. The Fa% predictability was compared with BM-PAMPA, DS-PAMPA, Caco-2 and immobilized liposome chromatography, resulting in promising predictability. 

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