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.

Ex vivo penetration of fosfomycin into healthy and Lawsonia intracellularis-colonized swine intestinal mucosa.

Fosfomycin (FOS) is an antibiotic used, mostly in Latin America, for the treatment of lung and enteric infections of pigs. Intracellular fluids of enterocytes can act as biophase for Lawsonia intracellularis, the causative agent of porcine proliferative enteropathy (PPE). The aim of this study was to determine whether the presence of L. intracellularis in the enterocytes modifies FOS penetration. Eight healthy pigs in growth-finishing stage were used to produce healthy (group A) and L. intracellularis-colonized (group B) intestinal explants. For both groups, treatment consisted of a 580 µg/ml concentration of calcium FOS, which was added to each explant (0.5-6 hr). For group B, the Enterisol Ileitis® vaccine was used as source of the micro-organism. Previously to the assay, the time necessary for L. intracellularis to colonize the enterocytes was defined. Also, a PCR protocol was optimized to determine the presence of the pathogen in the explants. There were nonstatistical differences for the penetration of the antibiotic into healthy and L. intracellularis-colonized enterocytes. MIC90 of FOS for L. intracellularis is unknown; nevertheless, MIC90 of various antibiotics ranges between 0.125 and 128 µg/ml. FOS reaches inside the enterocyte concentrations which surpass the MICs90 of other antibiotics that also act by the inhibition of cell wall synthesis; however, further studies should be carried out to determine fosfomycin MIC90 for L. intracellularis to discern the usefulness of this antibiotic in the treatment of PPE.