Antimicrobial agents are used extensively off‐label in mink, as almost no agents are registered for this animal species. Pharmacokinetic (PK) and pharmacodynamic (PD) data are required to determine antimicrobial dosages specifically targeting mink bacterial pathogens. The aims of this study were to assess, in a PKPD framework, the empirical dosage regimen for a combination of trimethoprim (TMP) and sulfadiazine (SDZ) in mink, and secondarily to produce data for future setting of clinical breakpoints. TMP and SDZ PK parameters were obtained experimentally in 22 minks following IV or oral administration of TMP/SDZ (30 mg/kg, i.e. 5 mg/kg TMP and 25 mg/kg SDZ). fAUC/MIC with a target value of 24 hr was selected as the PKPD index predictive of TMP/SDZ efficacy. Using a modeling approach, PKPD cutoffs for TMP and SDZ were determined as 0.062 and 16 mg/L, respectively. By incorporating an anticipated potentiation effect of SDZ on TMP against Escherichia coli and Staphylococcus delphini, the PKPD cutoff of TMP was revised to 0.312 mg/L, which is above the tentative epidemiological cutoffs (TECOFF) for these species. The current empirical TMP/SDZ dosage regimen (30 mg/kg, PO, once daily) therefore appears adequate for treatment of wild‐type E. coli and S. delphini infections in mink.

中文翻译：

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验证一种经验性磺胺嘧啶-甲氧苄啶给药方案，用于治疗水貂中的大肠杆菌和海豚葡萄球菌感染（Neovison vison）。

抗微生物剂在水貂中广泛使用，因为几乎没有针对该动物物种注册的药剂。需要药代动力学 (PK) 和药效学 (PD) 数据来确定专门针对水貂细菌病原体的抗菌剂量。本研究的目的是在 PKPD 框架中评估甲氧苄啶 (TMP) 和磺胺嘧啶 (SDZ) 组合在水貂中的经验给药方案，其次是为未来设置临床断点提供数据。TMP 和 SDZ PK 参数是在 IV 或口服 TMP/SDZ（30 毫克/千克，即 5 毫克/千克 TMP 和 25 毫克/千克 SDZ）后的 22 只貂中通过实验获得的。F选择目标值为 24 小时的 AUC/MIC 作为预测 TMP/SDZ 功效的 PKPD 指数。使用建模方法，TMP 和 SDZ 的 PKPD 临界值分别确定为 0.062 和 16 mg/L。通过结合 SDZ 对 TMP 对大肠杆菌和海豚葡萄球菌的预期增强作用，TMP的 PKPD 临界值被修改为 0.312 mg/L，高于这些物种的暂定流行病学临界值 (TECOFF)。因此，目前的经验性 TMP/SDZ 剂量方案（30 mg/kg，口服，每天一次）似乎足以治疗水貂的野生型大肠杆菌和海豚链球菌感染。