Antibiotics intestinal absorption

Tamai, I., et al. The predominant contribution of oligopeptide transporter PepTl to intestinal absorption of beta-lactam antibiotics in the rat small intestine. J. Pharm. Pharmacol. 

Ishizawa, T., et al. Mechanisms of intestinal absorption of the antibiotic, fosfomydn, in brush-border membrane vesicles in rabbits and humans./. Pharmacobiodyn. 1992, 25, 481-489. 

Various carboxylic acid salts have also been reported. Gallardo35 produced the maleate salt of neomycin which, it was claimed, improved the aqueous stability of the antibiotic. A practically tasteless compound, the citrate salt,has been described by Szyszka3 . Neomycin mandelate has been claimed to be particularly useful in the treatment of urogenital infections3 while the di-hydroxy-dinaphthylmethane-dicarboxylate4(3 and the pamoate salts43,67,68 have a low intestinal absorption and are thus effective treatments for intestinal infections. 

Biganzoli E, Cavenaghi LA, Rossi R, Brunati MC, Nolli ML (1999) Use of a Caco-2 cell culture model for the characterization of intestinal absorption of antibiotics. Farmaco 54 594-599. 

E. Nakashima, A. Tsuji, M. Nakamura, T. Yamana, Physicochemical Properties of Amphoteric beta-Lactam Antibiotics. IV. First- and Second-Order Degradations of Cefaclor and Cefatrizine in Aqueous Solution and Kinetic Interpretation of the Intestinal Absorption and Degradation of the Concentrated Antibiotics , Chetn. Pharrn. Bull. 1985, 33, 2098-2106. 

Yata N, Sugihara N, Yamajo R, et al. Enhanced small intestinal absorption of P-lactam antibiotics in rats in presence of monodesmosides from pericaps of Sapindus mukurossi (Ennmei-hi). J Pharmacobio-Dyn 1986 9 211-217. 

As recently as 1980 it was estimated that there were 100 million cases of acute diarrhea in Asia, Africa, and Latin America 3 in 1991 there were four million deaths among children under five years of age.b The causative agents are bacteria and one of the most dangerous is Vibrio cholerae, which multiplies in the small intestine and secretes an exotoxin. Cholera toxin causes such a rapid loss of fluid and salts from the body that death occurs very quickly, even in adults. There is little cellular damage and almost all deaths can be prevented by intravenous administration of water, salts, and the antibiotic tetracycline. Fluids can also be given orally if glucose, which promotes intestinal absorption, is included with the Na+, K+, Cl, and HC03 salts.b... 

As discussed in Section 13.3.5, ascorbate enhances the intestinal absorption of inorganic iron, and therefore it is frequently prescribed together with iron supplements. It is also used when it is desired to acidify the urine (e.g., in conjunction with some antibiotics). Supplements of vitamin C (often of the order of grams per day) are widely consumed to protect against cancer, cardiovascular disease, and viral infections, although (as discussed below) the evidence of efficacy is poor. 

Because of its potential toxicity, vancomycin is reserved for serious infections in which less toxic antibiotics are ineffective or not tolerated. Generally, vancomycin is administered intravenously because of poor intestinal absorption. It is the drug of choice for treating infections caused by methicillin-resistant staphylococci and penicillin-resistant Streptococcus pneumoniae. Vancomycin has been used to treat enterococcal infections because of their resistance to the P-lactam antibiotics, but most enterococci are now also resistant to vancomycin. Oral administration of rancomycin is important for treatment of some gastrointestinal infections such as pseudomembranous colitis caused by C. difficile. 

Deficiencies are generally seen only after long antibiotic therapies, which deplete the intestinal fauna or following excessive consumption of raw eggs. The latter is due to the affinity of the egg white protein, avidin, for biotin preventing intestinal absorption of the biotin. 

In recent years, there has been increasing awareness regarding the importance of transporters in the absorption and disposition of NMEs. While the major portion of NMEs or marketed drugs traverse cell membranes by passive diffusion, there are numerous examples where the involvement of specialized transport mechanisms has been demonstrated. Examples include the role of oligopeptide transporters in the intestinal absorption of P-lactam antibiotics, angiotensinconverting enzyme (ACE) inhibitors, and novel NMEs as well as the role of P-glycoprotein (P-gp) in the secretion of molecules into the intestine [11,77—79]. Transfection of cells with the transporter protein of interest has permitted the evaluation of precise cellular mechanisms of uptake and transport of NMEs. Transfected cell lines by definition are tailor-made to overexpress the protein of... 

A Tsuji. Intestinal absorption of P-lactam antibiotics. In MD Taylor, GL Amidon, eds. Peptide-Based Drug Design. Washington DC American Chemical Society, 1995, pp 101—134. 

As indicated above, a large number of absorption enhancers including surfactants, bile salts, chelating agents, and fatty acids have been used to enhance the intestinal absorption of antibiotics and macromolecules [9, 22]. When these absorption en-... 

An understanding of osmosis and the intestinal absorption of salt and glucose forms the basis for a simple therapy that saves millions of lives each year, particularly in less-developed countries. In these countries, cholera and other intestinal pathogens are major causes of death of young children. A toxin released by the bacteria activates chloride secretion by the intestinal epithelial cells into the lumen water follows osmotlcally, and the resultant massive loss of water causes diarrhea, dehydration, and ultimately death. A cure demands not only killing the bacteria with antibiotics, but also rehydration— replacement of the water that is lost from the blood and other tissues. 

Kramer, W. Girbig, F. Gutjaha, U. Howalewski, S. Adam, F. Schiebler, W. Intestinal absorption of P-lactam antibiotics and oligopeptides—functional and stereoselective reconstitution of the oligopeptide transporter system from rabbit small intestine. Eur. J. Biochem. 1992, 204, 923-930. 

NaMshima, E., Tsuji, A., Kagatani, S., and Yamana, T., 1984, Intestinal absorption mechanism of amino-(3-lactam antibiotics. III. Kinetics of carrier-mediated transport across the rat small intestine in situ, J. Pharmacobio-Dyn. 7 452-464. 

A deficiency in the production of vitamin K may occur during intestinal dysbiosis (an impaired balance of the intestinal microflora), in inflammatory intestinal diseases (such as Crohn s disease), in intestinal absorption disorders and with an inadequate production of bile. Deficiency can be manifested by blood clotting disorders (this is rare in humans). Chickens are particularly sensitive to the lack of vitamin K, mainly due to the use of antibiotics that inhibit the activity of intestinal microflora. Vitamin K is therefore added to feed mixtures to prevent bleeding into the muscles and skin. 

Antibiotics (qv) have been fed at subtherapeutic levels to promote mminant animal growth. Possible reasons for the observed growth include decreased activity of microbes having a pathogenic effect on the animal, decreased production of microbial toxins, decreased microbial destmction of essential nutrients, increased vitamin synthesis or synthesis of other growth factors, and increased nutrient absorption because of a thinner intestinal wall... 

Sorbitan sesquioleate emulsions of petrolatum and wax are used as ointment vehicles in skin treatment. In topical appHcations, the inclusion of both sorbitan fatty esters and their poly(oxyethylene) derivatives modifies the rate of release and promotes the absorption of antibiotics, antiseptics, local anesthetics, vasoconstrictors, and other medications from suppositories, ointments, and lotions. Poly(oxyethylene(20)) sorbitan monooleate, also known as Polysorbate 80 (USP 23), has been used to promote absorption of ingested fats from the intestine (245). 

PJ Sinko, GL Amidon. Characterization of the oral absorption of P-lactam antibiotics. I. Cephalosporins Determination of intrinsic membrane absorption parameters in the rat intestine in situ. Pharm Res 5 645-650, 1988. 

Another type of intestinal peptide transporter, hPTl, which is significantly different in sequence from PEPT1, was identified using a functionally inhibitory monoclonal antibody [99]. This transporter is widely expressed in the human GI tract and facilitates the oral absorption of pdactam antibiotics and ACE inhibitors from the intestine [18, 99]. Interestingly, we recently reported that hPTl gene expression is approximately 4-fold higher than PEPT1 in the human duodenum [4] (Fig. 11.1). 

H. Saito, M. Okuda, T. Terada, S. Sasaki, and K. Inui. Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney. J Pharmacol Exp Ther 275 1631-1637 (1995). 

---