Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, 42031 Konya, Turkey.
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, 42031 Konya, Turkey.
J Dairy Sci. 2018 Dec;101(12):10694-10702. doi: 10.3168/jds.2018-14766. Epub 2018 Oct 11.
This study determined the distribution of drugs to different milk fractions according to their physicochemical properties. Hydrophilic drugs tend to concentrate in skim milk, whereas lipophilic drugs tend to concentrate in cream. The concentration of a drug in casein is related to its degree of binding to milk proteins. Thus, we aimed to determine whether withdrawal time in whole milk differs from that in cream, casein, and skim milk. Amoxicillin and tylosin were selected as prototype hydrophilic and lipophilic drugs, respectively. The study was conducted in vitro and in vivo to determine whether in vitro conditions reflect the distribution of drugs in the different milk fractions in vivo. The in vivo study was conducted using a crossover design on 6 healthy Holstein dairy cattle. First, amoxicillin (i.m., single dose, 14 mg/kg) was administered to cows. Following a 1-wk washout period, tylosin (i.m., single dose, 15 mg/kg) was administered. Concentrations of amoxicillin and tylosin in milk and milk fractions were measured using HPLC-UV. In the in vitro study, 0.04 to 400 μg/g of amoxicillin and 0.05 to 50 μg/g of tylosin were spiked to drug-free milk and the concentrations in milk and milk fractions were measured. In addition, the percentage of total protein in milk and milk fractions was determined. Amoxicillin accumulated more in skim milk than in cream and casein, both in vitro (92%) and in vivo (73%, skim milk-to-whole milk ratio). The distribution of tylosin in whole and skim milk was similar to that of amoxicillin in the in vitro study, in contrast to the accumulation of tylosin in cream seen in vivo. However, the accumulation ratio of tylosin in cream was lower than expected. By either method, tylosin was less concentrated in casein than in skim milk and cream. The percentage of total protein was similar in skim milk and whole milk and higher than in cream. Thus, amoxicillin accumulates less in cream and casein, suggesting that these fractions would pose a lower risk to the consumer. Tylosin was still present at the maximum residue limit (50 μg/kg) 24 h after injection in the casein fraction and 48 h after injection in the cream fraction.
本研究根据药物的物理化学性质确定了药物在不同乳成分中的分布。亲水性药物倾向于集中在脱脂乳中，而疏水性药物则倾向于集中在奶油中。药物在酪蛋白中的浓度与其与乳蛋白的结合程度有关。因此，我们旨在确定全脂奶与奶油、酪蛋白和脱脂奶的停药时间是否不同。阿莫西林和泰乐菌素分别被选为亲水性和疏水性原型药物。该研究在体外和体内进行，以确定体外条件是否反映了药物在体内不同乳成分中的分布。体内研究采用 6 头健康荷斯坦奶牛的交叉设计进行。首先，给奶牛肌肉注射阿莫西林（单剂量，14mg/kg）。经过 1 周的洗脱期后，肌肉注射泰乐菌素（单剂量，15mg/kg）。使用 HPLC-UV 测量牛奶和乳成分中的阿莫西林和泰乐菌素浓度。在体外研究中，向无药牛奶中添加 0.04 至 400μg/g 的阿莫西林和 0.05 至 5μg/g 的泰乐菌素，并测量牛奶和乳成分中的浓度。此外，还测定了牛奶和乳成分中总蛋白的百分比。阿莫西林在体外（92%）和体内（73%，脱脂奶与全脂奶的比例）在脱脂奶中的积累量多于在奶油和酪蛋白中的积累量。在体外研究中，泰乐菌素在全脂奶和脱脂奶中的分布与阿莫西林相似，而在体内观察到泰乐菌素在奶油中的积累。然而，泰乐菌素在奶油中的积累比例低于预期。无论是哪种方法，泰乐菌素在酪蛋白中的浓度都低于脱脂奶和奶油。脱脂奶和全脂奶中的总蛋白百分比相似，高于奶油。因此，阿莫西林在奶油和酪蛋白中的积累量较少，这表明这些成分对消费者的风险较低。泰乐菌素在酪蛋白中的残留量在注射后 24 小时仍达到最大残留限量（50μg/kg），在奶油中的残留量在注射后 48 小时仍达到最大残留限量。
