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

Abstract

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.

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

“…It is imperative to acquire and seriously ponder this information to support decisions on eligibility of antibiotic pharmaceutical formulations and the vehicle for their administration in order to harness the benefits of these drugs while taking responsibility on their use. The deleterious impact that water or feed components can have on antibiotic absorption and bioavailability have been previously demonstrated by other authors (Abuhelwa et al, 2017; Burow & Kasbohrer, 2016; Decundo et al, 2019; Ferran & Roques, 2019; Soraci et al, 2014; Vandael et al, 2019; Ziółkowski et al, 2016) and further confirmed in the present work. Thus, the incompatibility of a drug with its vehicle of administration would lead to erratic dosage, unpredicted therapeutic outcomes, environmental accumulation, and development of antimicrobial resistance.…”

Can oral group medication be improved to reduce antimicrobial use?

“…A recent study not only demonstrated that adding calcium carbonate to puriied water decreased the solubility of oxytetracycline, but also that water hardness could afect the bioavailability of oxytetracycline in piglets. 6 These indings highlight the necessity of regularly checking water quality and improving it if necessary. However, such checks seem to be performed rarely on most farms.…”

Balantidium coli in pig farms suspected of porcine circovirus type 2 (PCV2) associated enteritis

“…The diarrhoea that the three studied farms’ herds suffered highlights the importance of adequate water quality. It is known that it has a great impact on animal performance and production, affecting the solubility and bioavailability of antibiotics administered in it ( 5 , 12 ). For example, hardness is a critical aspect when automatic delivery systems are applied for drug administration, since certain antibiotics are prone to interact with cations forming insoluble complexes ( 5 , 12 ).…”

“…It is known that it has a great impact on animal performance and production, affecting the solubility and bioavailability of antibiotics administered in it ( 5 , 12 ). For example, hardness is a critical aspect when automatic delivery systems are applied for drug administration, since certain antibiotics are prone to interact with cations forming insoluble complexes ( 5 , 12 ). Moreover, it predisposes containers and pipelines to the formation of mineral deposits, resulting in decreased water flow and obstruction of drinkers and water nipples, as well as impeding absorption of antibiotics ( 5 ).…”