Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs

Abstract

The penetration of oxytetracycline (OTC) in plasma and nasal secretions of healthy pigs was evaluated during the first study, in response to oral dose of 20 mg of OTC per kg of body weight (bwt) per day as a 400 mg/kg feed medication (n = 5) and to intramuscular (i.m.)-administered formulations at 10 mg/kg bwt (n = 5), 20 mg/kg bwt (n = 5), 40 mg/kg bwt (n = 5). Concentrations of OTC in plasma and nasal secretions were determined by a validated ultra-high performance liquid chromatography associated to tandem mass spectrometry method (UPLC/MS/MS). The objectives were to select the efficacy treatment and to evaluate the possibility to predict nasal secretions concentrations from those determined in plasma. The animals were housed together in each experiment. In each group, the treatment was administered once daily during 6 consecutive days, and nasal secretions and plasma were collected after 4 and 24 h at day 2 and day 6. For oral administration, only one medicated feed was prepared and distributed to all the animals together and was consumed in approximately 1 h. To meet recommendations of efficacy for OTC in nasal secretions, only the i.m. of 40 mg/kg bwt associated to an inter-dosing interval of 24 h provides and maintains concentrations in nasal secretions ≥1 μg/mL, appropriate to the MIC 50 and 90 of Pasteurella multocida and Bordetella bronchiseptica, respectively, the main pathological strains in nasal secretions. It has been demonstrated that, using a generalized linear mixed model (GLMM), OTC in the nasal secretions (μg/mL) can be predicted taking into account the OTC concentrations in plasma (μg/mL), according to the following equation: OTC(nasal secretions) = 0.28 OTC(plasma) -1.49. In a second study, the pharmacokinetic behaviour of OTC in plasma and nasal secretions of healthy pigs was investigated, after single-dose i.m. of 40 mg/kg bwt of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. The data collected in 10 pigs for OTC were subjected to non-compartmental analysis. In plasma, the maximum concentration of drug (C(max) ), the time at which this maximum concentration of drug (T(max) ) was reached, the elimination half-life (t½) and the area under the concentration vs. time curve (AUC) were, respectively, 19.4 μg/mL, 4.0, 5.1 h and 150 μg·h/mL. In nasal secretions, C(max) , T(max) , t½ and AUC were, respectively, 6.29 μg/mL, 4.0, 6.6 h and 51.1 μg·h/mL.

Assessment of the Impact of Potential Tetracycline Exposure on the Phenotype of Aedes aegypti OX513A: Implications for Field Use

“…We found that feeding adult females 50 μg mL -1 or 100 μg mL -1 chlortetracycline in both blood and sugar water did not lead to increased survival of their progeny. The highest dose of chlortetracycline used in this study was 10-fold higher than the normal concentration found in the blood of humans or animals receiving usual therapeutic doses of tetracyclines, and 5-fold higher than the highest dose reported from any animal blood [ 27 ]. These data therefore disprove the hypothesis that a female can deliver enough tetracycline to her progeny to allow increased survival rates through biting a human or animal on a normal therapeutic dose of tetracycline.…”

“…In mammals the concentration of tetracycline compounds in the blood usually reaches a peak 2 to 6 hours following an oral or injected dose, and then gradually declines due to the body’s metabolic activity [ 26 ]. In both humans and livestock, the peak concentration of tetracyclines in blood (plasma) following a standard therapeutic dose normally remains below 10 μg ml -1 [ 26 , 27 ]. We found that feeding adult females 50 μg mL -1 or 100 μg mL -1 chlortetracycline in both blood and sugar water did not lead to increased survival of their progeny.…”

“…Eggs were collected. Chlortetracycline concentrations were chosen to reflect levels well above the maximum recorded plasma levels following a therapeutic treatment with tetracyclines [ 26 , 27 ].…”

Use of antimicrobial agents in livestock

“…Antimicrobial agents are widely distributed in livestock species as well. Following intramuscular injection of pigs, enrofloxacin (26) and oxytetracyline (25) are present in nasal secretions at concentrations approximately the same as (enroflaxacin) or one third of (oxtetracycline) those in plasma. Fluoroquinolones are substrates for membrane transporters which are responsible for efflux into the gut (5) and into the ruminant mammary gland (210).…”

Correlation between oral fluid and plasma oxytetracycline concentrations after intramuscular administration in pigs

“…Values of elimination half‐life seem to show variability between studies. In most studies, collection of plasma samples was shorter (i.e., up to 84 hr or 6 days in Archimbault et al., and Bimazubute et al., studies respectively) than in presented work, where plasma was sampled for 21 days.…”