Oxytetracycline bioavailability

Residues at the site of injection present specific problems. The persistence of residues at intramuscular injection sites may be due in part to the irritant response produced in the muscle. Chloramphenicol, tylosin, penicillins, dihydrostreptomycin and oxytetracycline have been shown to produce local irritation at the site of injection leading to residues persistence and this may be exacerbated by the solvent used (47-49) with one oxytetracycline product which produced little irritation, residues did not persist (49). Large variations in pharmacokinetic behaviour were noted in addition to the persistence at the injection site and in particular with oxytetracycline, bioavailability was reduced. These studies demonstrate the usefulness of pharmacokinetic data when studying specific routes of administration, and in particular they demonstrate the need to take into account other biological phenomena when attributing withdrawal periods, in this case, irritation at the injection site. The new draft EC Guideline requires that injection sites are examined in residues studies with injectable products and in the case of persistence at the site, then the withdrawal period will be based on this. 

Its bioavailability lo fish is favorable in comparison with other antibacterials such as oxytetracycline, which was used extensively in European aquaculture during the 1980s. The bioavailability of flumequine to Atlantic salmon was determined to be 40-45%, while that of oxytetracycline was only 1-5% when both compounds were administered orally to fish (158-161). 

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

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. 

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. 

Moderate variability in absorption of oxytetracycline from different intramuscular injection sites in calves was reported by Nouws and Vree. Bioavailability values of 79%, 86%, and 89% were obtained for injection into the buttock, neck, and shoulder, respectively. The same group reported variable bioavailability and residue profiles with 10 formulations of oxytetracycline in pigs and 5 formulations in calves, sheep, and pigs. ... 

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). 

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