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The pharmacokinetics of doxycycline was investigated in lactating sheep and lambs after oral administration at a dose of 10 mg/kg. Concentrations in plasma and milk were assayed with HPLC-PDA analysis. Doxycycline penetrates into the milk, and levels (0.38 ± 0.21 μg/ml) were found 0.5 hr after the treatment. The results suggest that the lambs can be exposed to doxycycline by suckling milk from their treated mothers. Population pharmacokinetic analysis showed a positive relationship between age, which reflects the stage of development of rumen function, and clearance. Possible explanations for the observed differences include the undeveloped rumen in lambs, the differences in the feed and liver function as evidenced by the blood biochemical parameters aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which were significantly lower in lambs (62.67 ± 27.83 U/L and 8.50 ± 6.80 U/L) than in sheep (114.33 ± 20.77 U/L and 18.00 ± 3.16 U/L)., (© 2020 John Wiley & Sons Ltd.)

Biofilm-forming bacteria are associated with difficult-to-cure bacterial infections in veterinary patients. According to previous studies, N-acetyl-L-cysteine (NAC) showed an inhibitory effect on biofilm formation when it was applied in combination with beta-lactam antibiotics and fluoroquinolones. The lack of information about the effect of NAC on doxycycline activity against biofilm-forming strains was the reason for conducting this study. Staphylococcus aureus (S. aureus) ATCC 25923, Staphylococcus aureus O74, Escherichia coli (E. coli) ATCC 25922 and Pseudomonas aeruginosa (P. aeruginosa) ATCC 27853 were used to evaluate the activity of doxycycline with and without addition of NAC on planktonic bacteria and on biofilm formation. The minimum inhibitory concentrations (MICs) of doxycycline were not affected by NAC for Gram-negative strains and were found to be two times higher for the strains of S. aureus. The minimum biofilm inhibitory concentrations (MBICs) for Gram-negative bacteria (2 μg/mL for E. coli ATCC 25922 and 32 μg/mL for P. aeruginosa ATCC 27853), determined using a standard safranin colorimetric assay, were higher than the MICs (0.5 and 4 μg/mL, respectively). The data suggest that the combinations of doxycycline and NAC could stimulate the growth of planktonic cells of S. aureus and biofilm-forming E. coli ATCC 25922. NAC did not affect the strong inhibitory effect of doxycycline on the biofilm formation by the strains of S. aureus. [ABSTRACT FROM AUTHOR]

Orally administered tetracycline antibiotics interact with feed, which may impact their bioavailability and efficacy. Therefore, the pH-dependent adsorption of doxycycline and its interaction with feed for ruminants was studied in vitro. Adsorption experiments on animal feed (135 and 270 mg) with initial doxycycline concentrations of 35, 75, and 150 µg/mL were performed. Desorption experiments were conducted by agitation of a predetermined mass of doxycycline-loaded animal feed in PBS, at pH = 3.0, 6.0, and 7.4, to simulate changes in the gastrointestinal tract. Antibiotic concentrations were determined by LC-MS/MS analysis. The adsorption/desorption of doxycycline was described by mathematical models. Chemisorption with strong intermolecular interactions between the active functional groups of doxycycline and the organic biomass was found. The experimental release curve comprised three sections: initial prolonged 27–30% release (pH = 6.0), followed by moderate 56–59% release (pH = 3.0), and final 63–74% release (pH = 7.4). The sigmoidal model showed a considerable role of diffusion with an initial prevalence of desorption and a decreased desorption rate thereafter. The Weibull equation revealed an initial release stage followed by a lag time section and sustained release. The study of doxycycline adsorption by the animal feed proved a maximum 80% encapsulation efficiency and revealed initial diffusion followed by chemisorption. The highest release efficiency of 74% suggests high bioavailability of doxycycline after oral administration in ruminants. [ABSTRACT FROM AUTHOR]

Mycoplasmosis is a bacterial infection that significantly affects poultry production, and it is often controlled with antibiotics, including doxycycline. The conducted study aimed to determine population pharmacokinetic (PopPk) parameters of doxycycline in healthy (n = 12) and in Mycoplasma gallisepticum-challenged (n = 20) chickens after its oral administration via drinking water at the registered dose rate of 20 mg/kg b.w./24 h for five days, without or with co-administration of N-acetylcysteine (NAC, a dose of 100 mg/kg b.w./24 h) via the feed. Doxycycline concentrations in plasma were analyzed with the LC-MS/MS method. The values of tvV/F and tvke were 4.73 L × kg−1 and 0.154 h−1, respectively, and they showed low BSV. A high BSV of 93.17% was calculated for the value of tlag of 0.8 h, which reflects the inter-individual differences in the water consumption. PTA was computed after Monte Carlo simulation with the registered dose for doxycycline. The target of %fT > MIC ≥ 80% and 100% can be achieved in 90% of the broiler population, after a correction for protein binding, for bacteria with MIC ≤ 0.5 mg × L−1 and 0.25 mg × L−1, respectively. The applied PopPk model did not reveal significant effect of M. gallisepticum infection and co-administration of NAC on pharmacokinetic parameters of doxycycline. [ABSTRACT FROM AUTHOR]

Background: Extensive interaction between gut microbiota and the host immune system has significant impact on chicken performance. Objective: Therefore, the influence of doxycycline, administered with or without Lactobacillus spp., on PepT1 and LEAP-2 mRNAs expression in duodenum, jejunum and liver was investigated in Duc chickens. Methods: One-day-old Duc broiler chickens were divided in four groups. Chickens without treatment served as controls. Five days after hatching the second group was treated with Lactobacillus brevis, L.plantarum and L.bulgaricus probiotics via feed for 15 days. The third group was treated with probiotics (as in group 2) and doxycycline (10 mg/kg bw, via drinking water for five days, started 15 days after hatching). The fourth group received antibiotic only as described above. Water and food (broiler starter without drugs) were supplied ad libitum. Samples from liver, duodenum and jejunum were collected at the end of the treatment with doxycycline (21 days after hatching). Expression levels of LEAP-2 and PepT1 mRNAs were determined by qRT-PCR. Results: Doxycycline administered alone or in combination with probiotics, provoked a statistically significant upregulation of LEAP-2 mRNA in the liver and in the duodenum. Abundance of PepT1 mRNA was increased in the duodenum. Administration of doxycycline alone caused a moderate induction of LEAP-2 mRNA and down-regulation of PepT1 mRNA in the liver. Conclusion: Up-regulation of the studied antimicrobial peptides provoked by combination of Lactobacilli and doxycycline might be beneficial in terms of host protection. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of doxycycline was investigated in force-fed and normally fed ducks after single intravenous (i.v.) and oral (p.o.) administration at a dose of 15 mg/kg bw. Serum concentrations of the drug were determined by the HPLC method. Pharmacokinetic parameters were calculated using compartmental analysis. Serum concentrations of doxycycline after i.v. administration in both groups were not statistically different. The values of half-lives were 5.82±1.85 h and 6.06±5.51 h in normal and force-fed birds. The total body clearance was respectively 0.40±0.05 L/h/kg and 0.34±0.10 L/h/kg, and volume of distribution (Vss) was 2.80±0.85 L/kg and 2.18±0.89 L/kg. After p.o. administraton the maximum serum levels in the control group were 0.70±0.12 μg/mL and in force-fed birds were 1.93±0.32 μg/mL, measured at 2.95±0.60 h and 1.45±0.24 h, respectively. The values of absolute bioavailability were 18.89±6.48% and 37.58±13.63%. Longer doxycycline retention in force-fed ducks was registered. Our data can be accepted as an information for possible prolonged retention of doxycycline in force fed ducks compared to normally fed ones. [ABSTRACT FROM AUTHOR]

Doxycycline is a well-tolerated tetracycline antibiotic, registered for use in rabbits and administered for treatment of bacterial infections in this animal species. Nevertheless, the available pharmacokinetic data are limited and this study aimed to investigate the pharmacokinetics of orally administered doxycycline in mature and immature rabbits by application of the population approach. The rabbits were treated orally with doxycycline hyclate (5 mg/kg bw) in the form of a solid gelatin capsules. Free plasma concentrations were determined with HPLC analysis with Photodiode array detection. The estimated typical value of volume of distribution (tvV), total body clearance, and absorption rate constant were 4.429 L/kg, 1.473 L/kg/h, and 0.257 h−1, respectively. The highest between-subject variability (BSV) of 69.30% was observed for tvV. Co-variates such as body weight, age, and biochemical parameters did not improve the tested model and did not contribute to explanation of the BSV. The population pharmacokinetic model of the orally administered doxycycline in rabbits should be further developed by addition of data from more animals treated with higher doses. An oral dose of 5 mg/kg could ensure percentage of the time from the dosing interval during which the concentration is above minimum inhibitory concentration (MIC) %fT > MIC of 35% if MIC of 0.18 μg·mL−1 and a dosing interval of 12 h is assumed which does not cover criteria for rational use of antibiotics. [ABSTRACT FROM AUTHOR]