Tetracyclines oral bioavailability

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. ... 

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

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). 

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. 

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. 

In chickens orally administered 10 mg/kg of the drug oxy-tetracycline with or without pretreatment with an extract of long pepper (equivalent to 15 mg/kg of piperine) daily for 7 days, an increase in bioavailability and decrease in the elimination rate of oxytetracycline was observed. Long pepper reduced the required loading and maintenance doses by 33.3 and 39%, respectively (Singh et al. 2005). 

The bioavailability of different specimens of a poorly soluble drug, when given orally and measured by the rate of the rise of plasma levels, varies enormously because of differing particle sizes. This test has revealed important differences between different brands of aspirin, diphenylhydantoin, cardiac glycosides (especially digoxin), tetracyclines, chloramphenicol, and dicumarol. The remedy is, usually supersonically micronize the drug. 

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