Facultad de Ciencias Agropecuarias, IRNASUS CONICET-Universidad Católica de Córdoba, Córdoba, Argentina.
Department of Pharmacology and toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Madrid, Spain.
J Vet Pharmacol Ther. 2021 Jan;44(1):68-78. doi: 10.1111/jvp.12900. Epub 2020 Aug 10.
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 hr , that is apparently higher than the reported for cows (0.13 L kg hr ) and pigs (0.16 L kg hr ). 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 8 hr and 5 mg kg 12 hr 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 12 hr by both routes should be recommended for Escherichia coli infections.
头孢喹肟是一种第四代头孢菌素，在山羊中被经验性地用于治疗。不同的生理因素，如妊娠或哺乳期，可能会影响药物在体内的药代动力学行为。本研究的目的是：（a）比较 2mg/kg 剂量静脉注射和肌肉注射后成年非妊娠（n=6）、妊娠（n=6）和哺乳期（n=6）山羊的头孢喹肟药代动力学，通过非线性混合效应模型进行丰富采样；（b）进行药代动力学/药效学分析，以评估不同生理状态下推荐剂量方案的疗效；（c）确定达到 PTA 值≥90%的最佳剂量方案，同时考虑 T>MIC≥60%的 MIC 值≤0.25μg/ml，在静脉和肌肉两种途径下的不同山羊亚群中。妊娠显著增加了 Ka 和 V1，而减少了 F0、Cl 和 Q。另一方面，哺乳期显著增加了 V1，减少了 Tk0。胎盘胎盘中的头孢喹肟浓度、羊水和胎儿血清表明穿过胎盘屏障的最小渗透。此外，头孢喹肟在牛奶中的渗透最小。山羊头孢喹肟的全身清除率为 0.29 L/kg/hr，明显高于牛（0.13 L/kg/hr）和猪（0.16 L/kg/hr）的报道。因此，与牛或猪相比，静脉和肌肉注射头孢喹肟的最佳剂量方案需要更高的剂量和给药频率。因此，静脉和肌肉注射的最佳剂量方案分别为 2mg/kg 8 小时和 5mg/kg 12 小时，可用于治疗多杀巴斯德菌和溶血支原体引起的呼吸道感染，但仅推荐这两种途径的 5mg/kg 12 小时用于治疗大肠杆菌感染。
