Tetracyclines bioavailability

Albert KS, Welch RD, De Sante KA, Disanto AR. Decreased tetracycline bioavailability caused by a bismuth subsalicylate antidarrheal mixture, JPharm Sci (1979) 68, 586-8. 

Healy DP, Dansereau RJ, Dunn AB, Clendening CE, Mounts AW, Deepe GS. Reduced tetracycline bioavailability caused by magnesium aluminum silicate in liquid formulations of bismuth suhszlicylzte. Ann PharmacoJter (1997) 31, 1460-4,... 

Absorbing or binding dragp to their surface, resulting in decreased bioavailability (eg, tetracycline)... 

Doxycycline tends to be more active against some bacteria than other tetracyclines. This is probably due to its slower excretion rather than to enhanced oral absorption. Doxycycline is used in cases where cost is unimportant. It is a very lipophilic drug that shows a high bioavailability, being almost completely absorbed after oral administration to different animal species except chickens (250, 251). 

Apart from being a diffusional barrier, mucin can also interact with drugs to decrease their bioavailability, as has been shown with tetracycline [106], phenylbutazone, and warfarin [107]. On the other hand, studies in rats showed that binding of some water-soluble drugs to intestinal mucus was essential for their absorption and that damage to the mucus significantly reduced absorption [108], The acidic mucus is essential for lipid absorption and could be important for the diffusion of lipophilic drugs (see below). 

Braybrooks, M.P., B.W. Barry, and E.T. Abbs. 1975. The effect of mucin on the bioavailability of tetracycline from the gastrointestinal tract in vivo, in vitro correlations. J Pharm Pharmacol 27 508. 

Diluents, although commonly presumed inert, do have the ability to influence the stability or bioavailability of the dosage form. For example, dibasic calcium phosphate (both anhydrous and dihydrate forms) is the most common inorganic salt used as a filler-binder for direct compression. It is particularly useful in vitamin products as a source of both calcium and phosphorous. Milled material is typically used in wet-granulated or roller-compacted formulations. The coarse-grade material is typically used in direct compression formulations. It is insoluble in water, but its surface is alkaline and it is therefore incompatible with drugs sensitive to alkaline pFI. Additionally, it may interfere with the absorption of tetracyclines [7]. 

Formation of soluble hydrochlorides of basic drugs does not necessarily result in improved bioavailability as was illustrated by comparative absorption studies of tetracyclines and lincomycin and their salts. " " Tetracycline-free bases gave higher plasma levels than their hydrochloride salts, while lincomycin hydrochloride had a lower bioavailability than the hexadecylsulfa-mate salts. These differences have been attributed to a common ion effect with gastric HCl following oral administration. 

Doxycycline can cause nausea, vomiting, and diarrhea. The bioavailability of doxycycline is reduced if coadministered with multivalent ions such as iron or magnesium. However, unlike tetracycline, it can be administered with food and dairy products. In addition, patients taking tetracyclines may experience photosensitivity, especially if they are fair skinned. Patients taking tetracyclines should avoid prolonged exposure to sunlight. 

Drug interactions The bioavailability of tetracyclines is significantly deaeased when administered with antacids containing aluminum, calcium, or magnesium, with iron-containing products, or with food. Food or dairy products do not affect the bioavailability of doxycycline or minocycyline. 

In the presence of moisture, calcium salts may be incompatible with amines, amino acids, peptides, and proteins, which may form complexes. Calcium salts will interfere with the bioavailability of tetracycline antibiotics. It is also anticipated that calcium sulfate would be incompatible with indomethacin, aspirin, aspartame, ampicillin, cephalexin, and eryth-romycin " " since these materials are incompatible with other calcium salts. 

Magnesium silicate may decrease the oral bioavailability of drugs such as mebeverine hydrochloride, sucralfate, and tetracycline, via chelation or binding, when they are taken together. The dissolution rate of folic acid, erythromycin stearate, paracetamol, " and chloroquine phosphate, " may be retarded by adsorption onto magnesium silicate. Antimicrobial preservatives, such as parabens, may be inactivated by the addition of magnesium silicate. ... 

The product labeling states that the simultaneous administration of sucralfate may reduce the bioavailability of certain agents (e.g.. tetracycline, phenytoin. digoxin. orcimelidine). It further recommends restoration of bioavailability by separating administration of the.se agents from that of sucralfate by 2 hours. Presumably, sucralfate binds these agents in the GI tract. 

Antibiotics (selected) Potential for reduced bioavailability due to complexation of drug with divalent and trivalent cations found in enteral feeding May influence quinolone antibiotics, penicillin, tetracycline, isoniazid, and rifampin Consider holding tube feeding before and after administration Avoid jejunal administration of ciprofloxacin Monitor clinical response... 

CAUTION. Bioavailability of digoxin gets altered due to the presence of such drugs as antacids, antineoplastic agents, cholestyramine resins, dietary fibre, erythromycin, neomycin, tetracyclines, metoclopramide, sulphasalazine and propantheline. 

Despite the fact that a plethora of dietary factors could, and will, affect the absorption characteristics of phytochemicals, this area has not been systematically explored. One reason might be the complexity of dietary factors and their interactions that could affect absorption. A nonexhaustive list would include the volume and composition of the food consumed, pH, caloric density, viscosity, nutrients (carbohydrates, protein, fat, fibers), alcohol, caffeine, and the presence of other phytochemicals. Such dietary factors affect the functional status, motility, and acidity of the gastrointestinal tract in a complex manner and modify the physicochemical properties, formulation, and dissolution characteristics of the compound of interest. Calcium in dairy products, for example, has the potential to chelate tetracyclines and fluoroquinolones and, thereby, reduce their bioavailability and biological activity [31]. 

TABLE 2.7 Oral Bioavailability of Tetracyclines (Mean Values of Studies Reported)... 

As tetracyclines have moderate to high lipophilic properties, the poor bioavailability associated with oral administration is somewhat surprising. Papich and Riviere suggest that causes may be multifactorial. As zwitterions, they are mainly ionized at pHs within GIT liquor. Moreover, feed reduces bioavailability, and tetracyclines chelate with polyvalent cations. Oxytetracycline absorption has been shown, experimentally, to be reduced by feed, dairy products, Ca +, Mg +, Al +, and Fe + ions and antacids. Even though doxycycline has a similar structure, affinity for metals is different from that of oxytetracycline with greater affinity for zinc and less for calcium. 

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