Transport cephalexin

Dantzig, A. H., Bergin, L., Uptake of cephalosporin, cephalexin, by a dipeptide transport carrier in the human intestinal cell line, Caco-2,... 

Chu, X. Y., et al. Correlation between epithelial cell permeability of cephalexin and expression of intestinal oligopeptide transporter. J. Pharmacol. Exp. Ther. 2001, 299, 575-582. 

Hu, M., et al. Mechanisms of transport of quinapril in Caco-2 cell mono-layers comparison with cephalexin. Pharm. Res. 1995, 12, 1120-1125. 

Some drugs with low intrinsic permeability achieve acceptable oral bioavailability because they are substrates for uptake transporters, which normally function in nutrient uptake. The most prominent example is the peptide transporter, PepTl, which is active toward peptidomimetic antibiotics such as cephalexin, the antiviral agent valacyclovir [24] and other drugs. PepTl is natively expressed in Caco-2 cells, and adenovirus transduction has been used to increase PepTl expression levels [25]. However, the expression of PepTl was not polarized in this system and this expressed system appears to be of limited value as an improved screening model. PepTl has also been expressed in Chinese hamster ovary cells and a variety of other mammalian systems [26, 27]. 

Koga K, Kawashima S, Murakami M (2002) In vitro and in situ evidence for the contribution of Labrasol and Gelucire 44/14 on transport of cephalexin and cefoperazone by rat intestine. Eur J Pharm Biopharm 54 311-318. 

Our studies on BLM system for separation of 7-ACA [23], cephalexin [24], CPC [26] using AHquat-336 as an anion exchange carrier revealed that pH gradient between the feed and stripping aqueous phases controlled the transport rate and separation efficiency. In some cases, uphill transport occurred with more than 90% recovery of cephalosporin molecules. BLM permeation study was also conducted for cephalothin, cefadroxil, cefazoHn, cefotaxim, cefaloridin, and 7-ACA for evaluation of initial flux. The initial permeation fluxes for various cephalosporins were well correlated with hydrophobicity [41] and the extraction equiHbrium constants. This seems to be in agreement with the idea that... 

The economic benefits alone are also driving the adoption of biotechnology. BASF has reduced the production process for Vitamin B2 from eight steps to one through biotechnology, while DSM s bioroute for Cephalexin has also substantially reduced the number of process steps. These examples and those of dozens of pharmaceutical intermediates demonstrate that cost savings of 50 percent and more are not unlikely. The savings may come directly from lower variable costs, but also from reduced capital expenditures for simpler production assets, or from reduced scale and therefore lower risk, transportation costs, and/or overcapacity. 

Figure 3 Correlation between the fraction absorbed and the membrane permeability in Caco-2 cells. Papp represents the membrane permeability of following 20 compounds, and was obtained by measuring the transcellular transport from the apical-to-basal side in Caco-2 cells. The fraction absorbed was obtained from literature. A amoxicillin, B antipyrine, C atenolol, D caffein, E cephalexin, F cyclosporin A, G enalaprilate, H L-glutamine, I hydrocortisone, J inulin, K D-mannitol, L metoprolol, M L-phenylalanine, N PEG-400, O PEG-4000, P propranolol, Q sucrose, R taurocholate, S terbutaline, T testosterone. Source From Ref. 37.

Sakane, T., Akizuki, M., Yoshida, M., Yamashita, S., Nadai, T., Hashida, M., and Sezaki, H. (1991), Transport of cephalexin to the cerebrospinal fluid directly from the nasal cavity, J. Pharm. Pharmacol., 43,449-451. 

Sugawara M, Iseki K, Miyazaki K, Shiroto H, Kondo Y, Uchino J. Transport characteristics of ceftibuten, cefixime and cephalexin across human jejunal brush-border membrane. J Pharm Pharmacol 1991 43(12) 882-4. 

The carrier-mediated uptake of p-aminohippuric acid (PAH) into BBMV (Figure 7) and PAH accumulation by renal cortical slices [69,77] were also significantly reduced by CPH treatment (1200 mg/kg/d for 3d). Furthermore, the transport of other cephalosporins across the renal brush border membrane is also affected by CPH-treatment the uptake of cephalexin and cefotiam into BBMV was greatly reduced whereas the uptake of CPH remained unaffected [77]. Secretion of cephalosporins across the brush border membrane is assumed to occur by the PAH-system as well as by the organic cation/H+-antiporter [127,133]. Reabsorption of many cephalosporins is performed by the dipeptide transport system [69, 133]. The unaffected uptake of CPH into BBMV from CPH-treated rats indicates that CPH is transported by a system different from the... 

The results of these studies showed significant inhibition of pahnitoylcarnitine-mediate respiration by cephaloridine in vitro, whereas cephaloglycin, which lacks structural homology with carnitine, caused a greater inhibition of the mitochondrial transport and oxidation of bufyrate than cephaloridine. It is possible that the mitochondrial uptake of butyrate was not affected by cephaloridine maybe because the pyridinyl nitrogen hinders its attack on the monocarboxylate receptors. Cephalexin induced only mild in vitro toxicity to the mitochondrial uptake and oxidation of bufyrate and palmitate [67]. 

Putnam, W.S., Pan, L., Tsutsui, K., Takahashi, L. and Benet, L.Z. (2002) Comparison of bidirectional cephalexin transport across MDCK and caco-2 cell monolayers interactions with peptide transporters. Pharmaceutical Research, 19, 27-33. 

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