Oxytetracycline formulations

Following intramuscular injection of a long-acting oxytetracycline formulation, all sheep tissue residues were below the US tolerance of 0.1 ppm by 14 days after treatment (235). After intramuscular administration to a dairy cow of a single dose of 5 mg oxytetracycline/kg bw, residues were present in milk for as long as 4 days after dosing at concentrations ranging from 370 ppb at day 1 posttreatment to 10 ppb at day 4 posttreatment (233). 

Table 6 Pharmacokinetic parameters describing the absorption and disposition of three oxytetracycline formulations administered intramuscularly (lateral neck) to pigs n — 8) at a dose of 20mg/kg body weight...

Nouws, J.F.M. Irritation, bioavailability and residue aspects of ten oxytetracycline formulations administered intramuscularly to pigs. Vet Q 1984, 6, 80-84. 

Banting, A. de L. Baggot, J.D. (1996) Comparison of the pharmacokinetics and local tolerance of three injectable oxytetracycline formulations in pigs. Journal of Veterinary Pharmacology and Therapeutics, 19, 50-55. 

Nouws, J.F.M. Vree, T.B. (1983) Effect of injection site on the bioavailability of an oxytetracycline formulation in ruminant calves. Veterinary Quarterly, 5, 165-170. 

George, L.W. Smith, J.A. (1985) Treatment of Moraxella bovis infections in calves using a long acting oxytetracycline formulation. Journal of Veterinary Pharmacology and Therapeutics, 8, 55-61. 

Fernandez-Gonzales et al. [16] described a method for determination of OTC in medicated premixes and feeds by second-derivative synchronous spectrofluorome-try. The assay based on the reaction of oxytetracycline with divalent metal ion (Ca2+) at pH 6-10 to form a yellow complex that can be analyzed by synchronous spectrofluorometry (AX = 115 nm). Rao et al. [17] described a spectrophotometric method for the determination of OTC in pharmaceutical formulations based on the color reaction with uranium, which was detected at 413 nm. 

Specialized antibiotic formulations have been developed for DCT, with physicochemical properties chosen to confer prolonged retention in the mammary secretions (21,, ). Ziv ( ) has summarized the desirable kinetic and other properties of such a product. The following antibiotic formulations are presently approved by the U.S. Center for Veterinary Medicine, FDA for infusion into the dry mammary gland erythromycin (300 mg), oxytetracycline-HCl (426 mg), benzathine cloxacillin (500 mg), cephapirin benzathine (300 mg), novobiocin (400 penicillin (200,000 lU) novobiocin (400 mg), penicil-... 

The first three of these agents to be discovered, tetracycline (1)chlortetracycline (2), and oxytetracycline (3), are subject to two major modes of degradation under conditions occurring during their isolation, purification, formulation, and administration. These are dehydration and epimerization. Each of these reactions leads to inactivation of the antibiotic thus, considerable effort has been expended in attempts to prevent or minimize these reactions. 

Neomycin is administered orally for treatment of bacterial infections of cattle, sheep, pigs, goats, and poultry at a dosage of 10 mg/kg bw. It is also used as a feed additive for growth-promoting purposes. Neomycin is further available alone or in combination with other drugs such as oxytetracycline, oleandomycin, lincomycin, and prednisolone, in intramammary formulations for treatment of mastitis. There has been relatively little clinical use of neomycin parenterally in animals because of the compound s reported nephrotoxicity and ototoxicity. 

Residue depletion studies in cattle, swine, sheep, chickens, and turkeys given oral forms of oxytetracycline including feed premixes, soluble powders, and tablets showed that residues in all edible tissues, with the exception of kidney, were cleared of detectable amounts of oxytetracycline within 5 days postdose. Injectable forms of oxytetracycline yielded higher residue levels that persisted longer than the oral forms, while long-acting formulations of oxytetracycline required extended withdrawal periods (234). 

A survey of veterinary drug use and residues in milk has been carried out in Hyderabad, India (34). The results of this survey showed that oxytocin and oxytetracycline were frequently used in veterinary formulations. As a result, a total of 9% of the marketed milk samples and 73% of the individual animal milk samples of the 205 milk samples analyzed in this survey contained oxytetracycline residues. Residual concentrations ranged from 0.2 to 1.4 ppm in marketed milk and from 0.2 to 6.7 ppm in samples obtained from individual buffaloes. In contrast, none of the government dairy samples analyzed was found to contain oxytetracycline residues. Maximum oxytetracycline intake by humans through consumption of such contaminated milk was calculated at the level of0.045 mg/kg body weight (bw)/day. 

The persistence of residues at intramuscular injection sites may be due in part to the irritant response produced in the muscle (52). Chloramphenicol, tylosin, penicillins, dihydrostreptomycin, and oxytetracycline have been shown to produce local irritation at the site of injection, leading to residue persistence this may be exacerbated by the solvent used. However, residues do not persist with proper injection of drugs and use of formulations that do not cause severe irritation (52), as has been demonstrated with one oxytetracycline product that produced little irritation (53-55). 

Tetracyclines mainly differ in their absorption after oral administration and their elimination. Absorption after oral administration is approximately 30% for chiortetracycline 60-70% for tetracycline, oxytetracycline, demeclocycline, and methacycline and 95-100% for doxycycline and minocycline. A portion of an orally administered dose of tetracycline remains in the gut lumen, modifies intestinal flora, and is excreted in the feces. Absorption occurs mainly in the upper small intestine and is impaired by food (except doxycycline and minocycline) by divalent cations (Ca2+, Mg2+, Fe2+) or Al3+ by dairy products and antacids, which contain multivalent cations and by alkaline pH. Specially buffered tetracycline solutions are formulated for intravenous administration. 

A 17-year-old girl, Miss EV, presents in your pharmacy with her regular prescription for Microgynon 30. Three months ago she had complained of problems of acne so you recommended that she try an over-the-counter topical benzoyl peroxide formulation. Her acne does not appear to have improved from the treatment so you recommend that she makes an appointment to see her GP. The following week she presents a new prescription for oxytetracycline tablets (500 mg b.d.). 

Doxycycline (a-6-deoxy-5-oxytetracycline monohydrate) is an antibiotic. U.S. 3,200,149 (to Pfizer) describes the preparation of the API and several formulations. Estimate the cost of producing the tablet formulation given in the patent. 

Domb, AJ. (1995) Long acting injectable oxytetracycline-liposphere formulation. Ini. J. Pharm. 124, 271-278. 

Tolymyxin B is formulated for delivery in combination with bacitracin, neomycin, gramicidin, oxytetracycline, or trimethoprim. See Chapters 43 through 46 for further discussion of these antibacterial agents. 

TETRACYCLINES ANTIVIRALS-DIDANOSINE i efficacy of tetracycline, and possibly demeclocycline, doxy-cycline, lymecycline, minocycline and oxytetracycline, with buffered didanosine Absorption may be affected by the buffered didanosine formulation, which t gastric pH Avoid co-administration with buffered didanosine preparations. Consider changing to enteric-coated didanosine tablets... 

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