Mileva Rositsa, Petkova Tsvetelina, Yaneva Zvezdelina, Milanova Aneliya
Department of Pharmacology, Animal Physiology, Biochemistry and Chemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria.
Antibiotics (Basel). 2023 Jan 28;12(2):268. doi: 10.3390/antibiotics12020268.
Orally administered tetracycline antibiotics interact with feed, which may impact their bioavailability and efficacy. Therefore, the pH-dependent adsorption of doxycycline and its interaction with feed for ruminants was studied in vitro. Adsorption experiments on animal feed (135 and 270 mg) with initial doxycycline concentrations of 35, 75, and 150 µg/mL were performed. Desorption experiments were conducted by agitation of a predetermined mass of doxycycline-loaded animal feed in PBS, at pH = 3.0, 6.0, and 7.4, to simulate changes in the gastrointestinal tract. Antibiotic concentrations were determined by LC-MS/MS analysis. The adsorption/desorption of doxycycline was described by mathematical models. Chemisorption with strong intermolecular interactions between the active functional groups of doxycycline and the organic biomass was found. The experimental release curve comprised three sections: initial prolonged 27-30% release (pH = 6.0), followed by moderate 56-59% release (pH = 3.0), and final 63-74% release (pH = 7.4). The sigmoidal model showed a considerable role of diffusion with an initial prevalence of desorption and a decreased desorption rate thereafter. The Weibull equation revealed an initial release stage followed by a lag time section and sustained release. The study of doxycycline adsorption by the animal feed proved a maximum 80% encapsulation efficiency and revealed initial diffusion followed by chemisorption. The highest release efficiency of 74% suggests high bioavailability of doxycycline after oral administration in ruminants.
口服四环素类抗生素会与饲料相互作用，这可能会影响其生物利用度和疗效。因此，本研究在体外考察了多西环素的pH依赖性吸附及其与反刍动物饲料的相互作用。采用初始多西环素浓度分别为35、75和150μg/mL的动物饲料（135和270mg）进行吸附实验。通过在pH = 3.0、6.0和7.4的磷酸盐缓冲盐溶液（PBS）中搅拌预先定量的负载多西环素的动物饲料进行解吸实验，以模拟胃肠道的变化。通过液相色谱-串联质谱（LC-MS/MS）分析测定抗生素浓度。采用数学模型描述多西环素的吸附/解吸过程。发现多西环素的活性官能团与有机生物质之间存在具有强分子间相互作用的化学吸附。实验释放曲线包括三个部分：初始阶段延长释放27-30%（pH = 6.0），随后是适度释放56-59%（pH = 3.0），最后是释放63-74%（pH = 7.4）。S形模型显示扩散起重要作用，初始阶段以解吸为主，随后解吸速率降低。威布尔方程显示出初始释放阶段，随后是滞后阶段和持续释放。动物饲料对多西环素吸附的研究证明包封效率最高可达80%，并显示出初始扩散随后是化学吸附。最高释放效率为74%，表明多西环素经反刍动物口服给药后具有较高的生物利用度。
