Cefquinome is a fourth‐generation cephalosporin that is used empirically in goats. Different physiologic factors like pregnancy or lactation could determine the pharmacokinetic behavior of drugs in the organism. The objectives of this study are to (a) compare the pharmacokinetics of cefquinome after intravenous and intramuscular administration in adult nonpregnant (n = 6), pregnant (n = 6), and lactating goats (n = 6), at a dose of 2 mg/kg, with rich sampling by nonlinear mixed‐effects modeling, (b) conduct a pharmacokinetic/pharmacodynamic analysis to evaluate the efficacy of the recommended posology in goats with different physiological states, and (c) determine the optimal posology that achieve a PTA value ≥ 90%, taking into account a T > MIC ≥ 60% of a MIC value ≤ 0.25 µg/ml, in the different subpopulations of goats for both routes. Gestation significantly increased Ka and V1, while reduced F0, Cl, and Q. On the other hand, lactation significantly increased V1 and reduced Tk0. Cefquinome concentrations achieved in placental cotyledon, amniotic fluid, and fetal serum indicate a minimal penetration across the placental barrier. Moreover, milk penetration of cefquinome was minimal. The total body clearance of cefquinome for goats was 0.29 L kg⁻¹ hr⁻¹, that is apparently higher than the reported for cows (0.13 L kg⁻¹ hr⁻¹) and pigs (0.16 L kg⁻¹ hr⁻¹). So, the optimal dose regimen for cefquinome after intravenous and intramuscular administration required higher dose and frequency of administration compared with recommendations for cows or pigs. Therefore, 2 mg kg⁻¹ 8 hr⁻¹ and 5 mg kg⁻¹ 12 hr⁻¹ could be used for IV and IM routes, respectively, for the treatment of respiratory infections caused by P. multocida and M. haemolytica, but only 5 mg kg⁻¹ 12 hr⁻¹ by both routes should be recommended for Escherichia coli infections.

中文翻译：

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通过静脉内和肌肉内给药后非妊娠、妊娠和哺乳期山羊头孢喹诺的非线性混合效应模型比较药代动力学和药代动力学/药效学分析。

头孢喹诺是第四代头孢菌素，经验用于山羊。怀孕或哺乳等不同的生理因素可以决定药物在生物体内的药代动力学行为。本研究的目的是 (a) 比较在成年非妊娠 ( n  = 6)、妊娠 ( n  = 6) 和哺乳山羊 ( n ) 中静脉和肌肉注射头孢喹诺后的药代动力学 = 6)，在 2 mg/kg 的剂量下，通过非线性混合效应模型进行丰富的采样，(b) 进行药代动力学/药效学分析，以评估推荐剂量对不同生理状态山羊的疗效，以及 (c) ) 确定实现 PTA 值 ≥ 90% 的最佳剂量，考虑到 T > MIC ≥ MIC 值 ≤ 0.25 µg/ml 的 60%，在两种途径的不同山羊亚群中。妊娠显着增加了 Ka 和 V1，同时降低了 F0、Cl 和 Q。另一方面，哺乳显着增加了 V1 并降低了 Tk0。在胎盘子叶、羊水和胎儿血清中达到的头孢喹诺浓度表明穿过胎盘屏障的渗透最小。此外，头孢喹诺的牛奶渗透是最小的。头孢喹诺对山羊的全身清除率为 0.29 L kg^-1  hr ^-1，这明显高于报告的奶牛（0.13 L kg ^-1  hr ^-1）和猪（0.16 L kg ^-1  hr ^-1）。因此，与牛或猪的建议相比，静脉和肌肉注射后头孢喹诺的最佳剂量方案需要更高的剂量和给药频率。因此，2 mg kg ^-1  8 hr ^-1和5 mg kg ^-1  12 hr ^-1可分别用于IV和IM途径，用于治疗多杀疟原虫和溶血支原体引起的呼吸道感染，但仅5 毫克公斤^-1  12 小时对于大肠杆菌感染，应推荐两种途径的^-1。