The vehicle of administration, feed or water, and prandial state influence the oral bioavailability of amoxicillin in piglets.

Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin's in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed. Then, pharmacokinetic parameters and bioavailability were determined in fasted and fed pigs using soft water, hard water, or feed as vehicles of administration following a balanced incomplete block design. Amoxicillin showed similar dissolution profiles in soft and hard water, distinct from the dissolution profile obtained with purified water. Complete dissolution was only achieved in purified water, and merely reached 50% in soft or hard water. Once dissolved, antibiotic concentrations decreased by around 20% after 24 h in all solutions. Korsmeyer-Peppas model best described amoxicillin release from feed in simulated gastric and intestinal media. Feed considerably reduced antibiotic dissolution in both simulated media. In vivo, amoxicillin exhibited significantly higher bioavailability when delivered via water to fasted than to fed animals, while in-feed administration yielded the lowest values. All treatments showed a similar rate of drug absorption. In conclusion, we demonstrated that water and feed components, as well as feed present in gastrointestinal tract of piglets decrease amoxicillin´s oral bioavailability. Therefore, the use of oral amoxicillin as a broad-spectrum antibiotic to treat systemic infections in pigs should be thoroughly revised.

Citrullinemia is a suitable biomarker for post weaning performance in piglets under intensive farming.

OBJECTIVE: To describe citrullinemia profiles during the weaning transition and correlate citrulline production with stress and growth in a commercial pig farm. ANIMALS: 240 healthy piglets of homogenous weight, weaned from second and third parity sows, were selected at weaning and subjected to the farm's routine management practices in May to July 2020 and May to July 2021. PROCEDURES: Piglets were weighed at weaning, then 15 and 49 days later in order to calculate daily weight gain during the first 15 and 49 days after weaning. Blood samples were collected from each piglet to determine citrulline and cortisol profiles during the early postweaning period. RESULTS: Citrullinemia decreased dramatically during the first week postweaning and then increased progressively to reach preweaning values by 15 days postweaning. Citrulline production during the first 2 weeks postweaning was negatively correlated with cortisol production (r: -0.2949) and positively correlated with mean daily weight gain during the first 15 (ρ: 0.5450) and 49 (ρ: 0.6603) days postweaning. CLINICAL RELEVANCE: Citrullinemia profile of piglets during the early postweaning period showed a temporal negative impact of stress (assessed by plasmatic cortisol levels) on intestinal enterocytes' mass and function, which resulted in a lower average daily weight gain. We demonstrated that a single biomarker, plasmatic citrulline, is useful to describe intestinal metabolism during the early postweaning period and that the greater the citrulline production during the first days after weaning, the higher the weight gain during the entire postweaning period.

Potential interactions between an oral fosfomycin formulation and feed or drinking water: Impact on bioavailability in piglets.

Feed and drinking water are the most frequently used vehicles for administration of antibiotics in intensive pig production. Interactions of drugs with feed and water components may affect dissolution and bioavailability. Therefore, antibiotic formulations should be tested in order to assure their suitability for oral use. In this study, an oral fosfomycin (FOS) formulation was evaluated considering dissolution in water (soft and hard), release kinetics from feed in simulated gastrointestinal fluids and bioavailability after oral administration blended into feed or dissolved in water (soft and hard), to fed and fasted piglets. FOS reached immediate dissolution in soft and hard water. The presence of feed significantly decreased antibiotic dissolution in simulated intestinal medium. Bioavailability was lower when feed was used as a vehicle for FOS administration than when the drug was dissolved in water (soft or hard). The fed or fasted condition of piglets did not affect bioavailability. Probably, FOS interactions with feed components alter its dissolution in the gastrointestinal tract, and only a fraction of the dose would be available for absorption. This information must be considered to support decisions on eligibility of antibiotic pharmaceutical formulations and the vehicle for their administration in order to pursue a responsible use of antibiotics.

Impact of water hardness on oxytetracycline oral bioavailability in fed and fasted piglets.

Water hardness is a critical factor that affects oxytetracycline dissolution by chelation with cations. These interactions may lead to impaired dosing and consequently decrease absorption. Moreover, feed present in gastrointestinal tract may interact with antibiotic and alter pharmacokinetic parameters. In the present study, dissolution profiles of an oxytetracycline veterinary formulation were assessed in purified, soft and hard water. Furthermore, oxytetracycline absolute bioavailability, after oral administration of the drug dissolved in soft or hard water, was evaluated in fed and fasted piglets. A maximum dissolution of 86% and 80% was obtained in soft and hard water, respectively, while in purified water dissolution was complete. Results from in vivo study reconfirmed oxytetracycline's very low oral bioavailability. The greatest values were attained when antibiotic was dissolved in soft water and in fasted animals. Statistically significant lower absolute bioavailability was achieved when hard water was used and/or animals were fed. Moreover, Cmax attained in all treatments was lower than MIC90 of most important swine pathogens. For these reasons, the oral use of OTC formulations, that have demonstrated low oral bioavailability, should be avoided to treat systemic diseases in pigs.

Effect of fosfomycin, Cynara scolymus extract, deoxynivalenol and their combinations on intestinal health of weaned piglets.

Weaning is a challenging stage of pig farming. Animals undergo environmental, social and dietary changes leading to weaning stress syndrome. In order to compensate for the detrimental effects of weaning stress, antibiotics and natural extracts are used as feed additives, sometimes without fully understanding the interactions between them or even with low concentrations of mycotoxins that are frequently present in feed. The aim of this study was to evaluate the effect of fosfomycin (FOS), Cynara scolymus extract (CSE), deoxynivalenol (DON) and their combined administration on intestinal health of weaned piglets. The experiment was designed as a 2 × 2 × 2 factorial arrangement with 3 factors (FOS, CSE and DON treatments), 2 levels each (presence and absence) and 3 repeats. Weaned piglets (n = 24) were randomly divided in groups to receive the different treatments, namely DON administered in diet (50 µg/kg BW), FOS administered into the drinking water (30 mg/kg BW), CSE administered in diet (15 mg/kg BW) and all their combinations. After 15 d, the animals were euthanized and gastrointestinal tract samples were immediately taken to evaluate gastrointestinal pH, Enterobacteriaceae to lactic acid bacteria (E:L) ratio, volatile fatty acid (VFA) concentrations, disaccharidase (lactase, sucrase and maltase) activity, histology (intestinal absorptive area [IAA] and goblet cells count) and mucus ability to adhere pathogenic Escherichia coli. From our results, FOS and CSE treatments, individually or combined, produced a lower E:L ratio, an enhanced production of butyrate, increased disaccharidase activity (particularly maltase), and a greater IAA and goblet cells count along with an increase in pathogenic bacteria adherence to intestinal mucus. Deoxynivalenol did not show interactions with the other factors and its administration produced decreases on VFA, disaccharidase activity and goblet cells count. In conclusion, weaning piglets receiving diets containing FOS, CSE or both exhibited evident beneficial intestinal effects compared to animals receiving diets free from these compounds. On the contrary, the presence of DON at sub-toxic concentrations produced detrimental effects on intestinal health. The knowledge of the physiological and pathological gut changes produced by these compounds contributes to understand their potential productive consequences.

Zearalenone adsorption capacity of lactic acid bacteria isolated from pigs

ABSTRACT The ability to adsorb zearalenone by five strain of lactic acid bacteria was evaluated: four strains of Lactobacillus spp. isolated from pig rectal swabs and one commercial strain (Lactobacillus rhamnosus). Several factors affecting the adsorption capacity were evaluated in order to improve the adsorption of the mycotoxin by bacteria. The stability of the zearalenone-bacteria complex was analyzed. In every case, bacterial adsorption capacity was higher than 40.0%. The strain showing the highest adsorption (68.2%) was selected for the following steps of this research. The adsorption percentages obtained after processing 6.5 and 7.5 mL MRS broth were 57.40% + 3.53 and 64.46% + 0.76, respectively. The stability of zearalenone-bacteria complex was evaluated by successively rinsing. In the first rinsing step 42.26% + 0.414 was still bound. In the second rinsing step 25.12% + 0.664 was still bound, whereas 15.82% + 0.675 remained in the pellet after the third rinse. Results obtained demonstrated that Lactic Acid Bacteria has capacity to adsorb zearalenone. Finally adsorption was increased using a higher volume of initial broth. These results could be used to design a new lyophilized powder for detoxification, using lactic acid bacteria as potential zearalenone adsorbents.

Zearalenone adsorption capacity of lactic acid bacteria isolated from pigs.

The ability to adsorb zearalenone by five strain of lactic acid bacteria was evaluated: four strains of Lactobacillus spp. isolated from pig rectal swabs and one commercial strain (Lactobacillus rhamnosus). Several factors affecting the adsorption capacity were evaluated in order to improve the adsorption of the mycotoxin by bacteria. The stability of the zearalenone-bacteria complex was analyzed. In every case, bacterial adsorption capacity was higher than 40.0%. The strain showing the highest adsorption (68.2%) was selected for the following steps of this research. The adsorption percentages obtained after processing 6.5 and 7.5mL MRS broth were 57.40%+3.53 and 64.46%+0.76, respectively. The stability of zearalenone-bacteria complex was evaluated by successively rinsing. In the first rinsing step 42.26%+0.414 was still bound. In the second rinsing step 25.12%+0.664 was still bound, whereas 15.82%+0.675 remained in the pellet after the third rinse. Results obtained demonstrated that Lactic Acid Bacteria has capacity to adsorb zearalenone. Finally adsorption was increased using a higher volume of initial broth. These results could be used to design a new lyophilized powder for detoxification, using lactic acid bacteria as potential zearalenone adsorbents.

Exposure variability of fosfomycin administered to pigs in food or water: impact of social rank.

The objective of this study was to document the effect of social ranking on the internal exposure of pigs to an antibiotic (fosfomycin) administered either in food or in drinking water. Signs of aggression were recorded at the feeder and drinker. The interindividual variability explained by the social rank was even greater when the test antibiotic was given in food despite the fact that the water consumption was less variable than the food intake. The range of plasma concentrations after administration of fosfomycin either in food or drinking water leads to a number of pigs in the treated group being exposed to rather low and highly variable concentrations of fosfomycin and not able to maintain adequate plasma concentrations above the typical minimum inhibitory concentration (MIC). Social rank clearly influences the level of exposure of pigs to fosfomycin both in food and drinking. However, its administration in drinking water is likely to be the best option to optimize antibiotic efficacy.

Penetration of fosfomycin into IPEC-J2 cells in the presence or absence of deoxynivalenol.

Fosfomycin (FOS) is an antibiotic used in pig farms for treatment and prevention of infections caused by resistant bacteria during the post-weaning period. Antibiotics and non-toxic concentrations of mycotoxins, such as deoxynivalenol (DON) are frequently found in the diet of animals. These compounds can establish interactions in the intestinal tract, which could affect and/or modify the penetration of FOS to enterocytes. The aim of this study was to determine the penetration of FOS into IPECJ-2 cells, a cell line derived from the small intestine of piglets, in the presence and absence of DON. The results from this study showed that there was statistically significant difference in the intracellular concentration of FOS between cells incubated with 580 µg/ml FOS and cells incubated with 580 µg/ml FOS and 1 µg/ml DON. The Cmax of the intracellular antibiotic in the culture plates incubated with FOS in absence of DON was 45.81 µg/ml with a tmax of 4 h. When IPEC-2 cells were incubated with FOS and DON the Cmax was 20.06 µg/ml and the tmax was 30 min. It is concluded that the non-toxic concentration of DON on IPEC-J2 cells after short-term exposure, interferes with the pharmacokinetics of the antibiotic.

Quantification of plasma reduced glutathione, oxidized glutathione and plasma total glutathione in healthy cats.

Glutathione is an important intracellular tripeptide with multiple functions. Abnormal glutathione metabolism is thought to play an important role in various diseases of cats. However, no data regarding concentration of plasma glutathione are available for domestic cats. This study discusses the development of a rapid, simple high pressure liquid chromatography method for measurement of reduced glutathione (GSH), oxidized glutathione (GSSH) and total glutathione (GSHt) in plasma, for the purpose of establishing baseline data for future studies. The mean concentrations of GSH, GSSH and GSHt were 4.51+/-1 microM; 19.44+/-3.79 microM (expressed as GSH equivalent) and 23.59+/-3.89 microM, respectively. This is the first report of plasma glutathione concentrations in this species.

Farmacocinética de cefoperazona en equinos

Los principales objetivos de este trabajo fueron: Determinar las características farmacocinéticas de cefoperazona en suero, liquido sinovial y orina luego de su administración IV. Determinar las características farmacocinéticas de cefoperazona en suero, liquidosinovial, esponja ósea, y orina luego de su administración IM. Determinar un plan terapéutico apropiado. En estos experimentos se trabajó con 6 equinos hembras de un peso aproximado de 405 + - 80 Kg, que recibieron cefoperazona a razón de 30 mg/Kg. El cronograma de extracción de las diversas muestras se presentan en la tabla XI. Las concentraciones de cefoperazona en suero, líquido sinovial, esponja ósea y orina fueron determinados microbiologicamente por el empleo de Bacillus subtilis ATCC como microorganismo test. El análisis farmacocinético de cefoperazone tras su administración IV e IM fue realizado a través de programas de iteración no lineal. El cálculo de las áreas bajo la curva de concentración tiempo fue realizado por el método de los tiempos de muestreo post aplicación de cefoperazona a razón de 30 mg/Kg en equinos. En base a los resultados obtenidos se puede concluír que luego de la administración de IV e IM de cefoperazona a razón de 30 mg/Kg se obtienen rápidos y óptimos niveles terapéuticos en suero, líquido sinovial, esponja ósea y orina superiores a la CIM (0.4 ,ug/ml) para bacterias de frecuente aparición en patologías infecciosas de los equinos durante un tiempo mínimo de 4 h

Farmacocinética de cefoperazona en equinos

Los principales objetivos de este trabajo fueron: Determinar las características farmacocinéticas de cefoperazona en suero, liquido sinovial y orina luego de su administración IV. Determinar las características farmacocinéticas de cefoperazona en suero, liquidosinovial, esponja ósea, y orina luego de su administración IM. Determinar un plan terapéutico apropiado. En estos experimentos se trabajó con 6 equinos hembras de un peso aproximado de 405 + - 80 Kg, que recibieron cefoperazona a razón de 30 mg/Kg. El cronograma de extracción de las diversas muestras se presentan en la tabla XI. Las concentraciones de cefoperazona en suero, líquido sinovial, esponja ósea y orina fueron determinados microbiologicamente por el empleo de Bacillus subtilis ATCC como microorganismo test. El análisis farmacocinético de cefoperazone tras su administración IV e IM fue realizado a través de programas de iteración no lineal. El cálculo de las áreas bajo la curva de concentración tiempo fue realizado por el método de los tiempos de muestreo post aplicación de cefoperazona a razón de 30 mg/Kg en equinos. En base a los resultados obtenidos se puede concluír que luego de la administración de IV e IM de cefoperazona a razón de 30 mg/Kg se obtienen rápidos y óptimos niveles terapéuticos en suero, líquido sinovial, esponja ósea y orina superiores a la CIM (0.4 ,ug/ml) para bacterias de frecuente aparición en patologías infecciosas de los equinos durante un tiempo mínimo de 4 h

Farmacocinética de cefoperazona en equinos

Los principales objetivos de este trabajo fueron: Determinar las características farmacocinéticas de cefoperazona en suero, liquido sinovial y orina luego de su administración IV. Determinar las características farmacocinéticas de cefoperazona en suero, liquidosinovial, esponja ósea, y orina luego de su administración IM. Determinar un plan terapéutico apropiado. En estos experimentos se trabajó con 6 equinos hembras de un peso aproximado de 405 + - 80 Kg, que recibieron cefoperazona a razón de 30 mg/Kg. El cronograma de extracción de las diversas muestras se presentan en la tabla XI. Las concentraciones de cefoperazona en suero, líquido sinovial, esponja ósea y orina fueron determinados microbiologicamente por el empleo de Bacillus subtilis ATCC como microorganismo test. El análisis farmacocinético de cefoperazone tras su administración IV e IM fue realizado a través de programas de iteración no lineal. El cálculo de las áreas bajo la curva de concentración tiempo fue realizado por el método de los tiempos de muestreo post aplicación de cefoperazona a razón de 30 mg/Kg en equinos. En base a los resultados obtenidos se puede concluír que luego de la administración de IV e IM de cefoperazona a razón de 30 mg/Kg se obtienen rápidos y óptimos niveles terapéuticos en suero, líquido sinovial, esponja ósea y orina superiores a la CIM (0.4 ,ug/ml) para bacterias de frecuente aparición en patologías infecciosas de los equinos durante un tiempo mínimo de 4 h