Tetracycline drugs administration

Report on the Status of the Food and Drug Administration s Proposed Withdrawal of Approvals for Low Level uses of Penicillin and Tetracyclines in Animal Feeds," Subcommittee on Agriculture, Rural Development and Related Agencies, 1985. 

Since 1969, the Food and Drug Administration s Center for Veterinary Medicine (formerly the Bureau of Veterinary Medicine) has had cause for concern that the subtherapeutic use of antibiotics in animal feeds may cause bacteria in animals to become resistant to antibiotics. This resistance to antibiotics is said by many knowledgeable scientists to be transferred to bacteria in humans, thus making these antibiotics ineffective in treating human bacterial infections due to compromise of therapy. For this reason, FDA proposed in 1977 to withdraw the use of penicillin in animal feed and restrict the use of the tetracyclines (chlortetracycline and oxytetracycline) to certain uses in animal feed. This talk will focus on FDA s efforts to finalize its review of the issue and present an update on the current status of the 1977 proposals. 

Totterman LE, Saxen L. Incorporation of tetracycline into human foetal bones after maternal drug administration. Acta Obstet Gynecol Scand 1969 48(4) 542-9. 

Oral administration of bicarbonate may decrease the absorption of ketoconazole. Increased blood levels of quinidine, flecainide, or sympatiiomimetics may occur when these agents are administered with bicarbonate There is an increased risk of crystalluria when bicarbonate is administered with the fluoroquinolones. Fbssible decreased effects of lithium, methotrexate, chlorpropamide, salicylates, and tetracyclines may occur when these drag s are administered with sodium bicarbonate. Sodium bicarbonate is not administered within 2 hours of enteric-coated drugs the protective enteric coating may disintegrate before the drug reaches the intestine. 

Absorption of antimicrobial agents such as fluoroquinolones and tetracyclines that can be bound by divalent and trivalent cations potentially could be compromised by administration with EN formulas containing these cations. The fluoroquinolones (e.g., levofloxacin and ciprofloxacin) have been best studied in this regard, and results of studies are not consistent. Mechanisms for an interaction between fluoroquinolones and EN formulas other than chelation by cations have been postulated.40 Some institutions hold tube feedings for 30 to 60 minutes or more before and after enteral dosages of fluoroquinolones. Because ciprofloxacin absorption has been shown to be decreased with jejunal administration, this drug probably should not be given by jejunal tube.41... 

Reduced absorption due to complex formation or other interactions between drugs and intestinal components leading to poor absorption has been described in a few cases. One example is the precipitation of cationic drugs as very poorly-soluble salts with bile acids, which has been reported for several compounds [62], Another well-known example is the complex formation between tetracycline together with calcium due to chelation after administration of the drug together... 

An important area of direct biochemical interference is that caused by fluorescent or fluorescent quenching materials in the blood or urine after the administration of a drug. These interferences may be observed during catecholamine analysis in urine from patients receiving -methyldopa, tetracyclines, chlortetracyclines, oxytetracycline, erythromycin, chlorpro-mazine, or quinidine (A2, G5). 

Upon oral administration, quinine effectively acts in combination with pyrimethamine, sulfadiazine, and/or tetracycline for treating uncomplicated incidents of chloroquine-resistant forms of P. falciparum. Because of the many associated side effects, its use is extremely limited. Currently, the only indication for use is for forms of malaria that are resistant to other synthetic drugs. Synonyms of this drug are bronchopulmin, nicopriv, quinnam, and others. 

These antibiotics are partially absorbed from the stomach and upper gastrointestinal tract. Food impairs absorption of all tetracyclines except doxycycline and minocycline. Absorption of doxycycline and minocy-cbne is improved with food. Since the tetracyclines form insoluble chelates with calcium (such as are found in many antacids), magnesium, and other metal ions, their simultaneous administration with milk (calcium), magnesium hydroxide, aluminum hydroxide, or iron will interfere with absorption. Because some of the tetracyclines are not completely absorbed, any drug remaining in the intestine may inhibit sensitive intestinal microorganisms and alter the normal intestinal flora. 

Atovaquone is poorly absorbed from the gastrointestinal tract, but absorption is increased with a fatty meal. Excretion of the drug, mostly unchanged, occurs in the feces. The elimination half-life is 2 to 3 days. Low plasma levels persist for several weeks. Concurrent administration of metoclopramide, tetracycline, or rifampin reduces atovaquone plasma levels by 40 to 50%. 

Physicochemical incompatibilities are of particular concern when parenteral administration is planned. For example, certain insulin preparations should not be mixed. Similarly, the simultaneous administration of antacids or products high in metal content may compromise the absorption of many drugs in the intestine, eg, tetracyclines. The package insert and the Handbook on Injectable Drugs (see References) are good sources for this information. 

After a single oral or intravenous administration of tetracycline to chickens at dosage rates of 100 mg/kg or 20 mg/kg bw, respectively, residue concentrations in muscle, kidney, and liver tissues were 0.03, 0.13, and 0.05 ppm, respectively, at 5 days posttreatment (248). Following intramuscular injection of tetracycline and oxytetracycline to goats at a dosage of 15 mg/kg bw at 24 h intervals for 4 days, residual levels of both drugs could be found in milk by day 4 after the last administration (249). The concentration of tetracycline at this time was 0.913 ppm, while that of oxytetracycline was 0.459 ppm in the milk. 

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). 

---