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.

饲料和水成分可能与药物相互作用并影响其溶解度和生物利用度。评估了给药载体（饲料和水）和断奶仔猪的膳食状况对阿莫西林口服生物利用度的影响。首先，评估了阿莫西林在纯净水、软水和硬水中的体外溶出度和稳定性，以及在模拟胃和肠介质中从饲料中的释放动力学。然后，按照平衡的不完全区组设计，使用软水、硬水或饲料作为给药载体，测定禁食和饲喂猪的药代动力学参数和生物利用度。阿莫西林在软水和硬水中显示出相似的溶出曲线，与用纯化水获得的溶出曲线不同。只有在纯净水中才能完全溶解，在软水或硬水中仅达到50%。一旦溶解，24 小时后所有溶液中的抗生素浓度均下降约 20%。 Korsmeyer-Peppas 模型最好地描述了阿莫西林在模拟胃和肠道介质中从饲料中的释放。饲料大大减少了抗生素在两种模拟介质中的溶解。在体内，通过水给予禁食动物时，阿莫西林表现出显着高于喂食动物的生物利用度，而饲料中给药产生的生物利用度最低。所有治疗均显示出相似的药物吸收率。总之，我们证明水和饲料成分以及仔猪胃肠道中存在的饲料会降低阿莫西林的口服生物利用度。因此，应彻底修改使用口服阿莫西林作为广谱抗生素治疗猪全身感染的做法。