RESUMEN

The objective of this study was to assess the impact of the vehicle of administration and the prandial state of post weaning piglets on the indices of therapeutic efficacy for different broad-spectrum antibiotic/pathogen combinations. Pharmacokinetic data were retrieved from previous studies, in which we orally administered oxytetracycline (OTC), fosfomycin (FOS), or amoxicillin (AMX) according to the following treatments: dissolved in soft water to fasted or non-fasted piglets, dissolved in hard water to fasted or non-fasted piglets, and mixed with feed. Minimum inhibitory concentration (MIC) values for susceptible strains of bacteria causing swine diseases were obtained from the database of European Committee on Antimicrobial Susceptibility Testing (EUCAST) for each antibiotic. Pharmacokinetic/pharmacodynamic (PK/PD) indices of therapeutic efficacy-drug exposure over the dosing interval (fAUC/MIC) for OTC and FOS; time that free drug concentration remains above MIC (%fT>MIC) for AMX-were calculated for each antibiotic/pathogen combination under each treatment. After all OTC and in-feed FOS and AMX treatments, the indices of therapeutic efficacy were below the target value for all the study microorganisms. When FOS or AMX were delivered dissolved in soft or hard water, the indices were above the target value over which therapeutic efficacy would be expected for Escherichia coli treated with FOS and, Glaesserella parasuis, Pasteurella multocida, and Actinobacillus pleuropneumoniae treated with AMX. The prandial state of piglets showed no influence on the indices of therapeutic efficacy. Pharmacokinetic profiles of broad-spectrum antibiotics, specifically the ability to achieve target concentrations, may be largely reduced due to drug interactions with components present in feed or water resulting in a discrepancy with PK/PD principles of prudent and responsible use of antibiotics.

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)