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首页> 外文期刊>Toxicological sciences: An official journal of the Society of Toxicology >Probabilistic Physiologically Based Pharmacokinetic Model for Penicillin G in Milk From Dairy Cows Following Intramammary or Intramuscular Administrations
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Probabilistic Physiologically Based Pharmacokinetic Model for Penicillin G in Milk From Dairy Cows Following Intramammary or Intramuscular Administrations

机译：乳房牛奶或肌肉内给药后奶昔牛奶中青霉素G的概率基础药代动力学模型

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摘要

Penicillin remains one of the most frequently identified violative drug residues in food-producing animals. The predominant violations of penicillin were found in cull dairy cows. In the United States, procaine penicillin G is approved to be used in dairy cows through intramuscular (IM) and intramammary (IMM) administrations. Physiologically based pharmacokinetic (PBPK) models are useful tools to predict withdrawal intervals and tissue residues of drugs in food animals to ensure food safety, especially for extralabel drug use due to the scarcity of experimental data after extralabel administrations. Currently, no PBPK model is available to predict penicillin concentrations in milk. A population PBPK model with a physiologically based compartment for the mammary gland was established for penicillin G in dairy cows. The model predicted the tissue and milk residues well based on comparison with data from previous pharmacokinetic studies. The predicted milk discard interval of procaine penicillin G administered at 10 times the label dose for 3 repeated IM administrations was 182 h, and 122 h at 4 times the label dose after 3 repeated IMM infusions. Predicted results showed that even 4 times label dose did not lead to violative tissue residues in healthy dairy cows with IMM infusions. The predominant violations found in cull dairy cows may be caused by altered pharmacokinetics due to mastitis, other diseases, and/or interactions with other drugs, which have impacts on penicillin distribution and elimination. The current PBPK model can help predict milk discard interval for penicillin following extralabel use through IM and IMM administrations.
机译：青霉素仍然是食品生产动物中最常见的血液残留物之一。在凯尔奶牛奶牛中发现了青霉素的主要侵犯。在美国，Procaine Penicillin G被批准通过肌肉内（IM）和内部（IMM）给药用于乳制品母牛。基于生理学的药代动力学（PBPK）模型是预测食物动物中药物的戒断间隔和组织残留的有用工具，以确保食品安全，特别是由于在额外标签主管机构后的实验数据稀缺而导致的extralabel药物使用。目前，没有PBPK模型可用于预测牛奶中的青霉素浓度。在奶牛中的青霉素G为青霉素G，在乳制品奶牛中建立了具有生理基础腺体隔室的人口PBPK模型。该模型基于与先前的药代动力学研究的数据的比较来预测组织和牛奶残留物。预测的牛奶丢弃在10倍的Procaine青霉素G的寄生额为3重复IM主管部门的标签剂量为182小时，并且在3重复的IMM输注后的标记剂量的4倍的122小时。预测结果表明，均匀4次的标记剂量均未导致健康乳制品奶牛中的血液组织残留物，具有免疫输注。在核心乳制品奶牛中发现的主要侵权可能是由于乳腺炎，其他疾病和/或与其他药物的相互作用而改变的药代动力学引起的，这对青霉素分布和消除产生了影响。目前的PBPK模型可以通过IM和IMM主管部门使用IM和IMM主管使用extralabel之后的青霉素预测预测青霉素的牛奶丢弃间隔。

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