Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Bukgu, Daegu, 41566, Republic of Korea.
Developmental and Reproductive Toxicology Research Group, Korean Institute of Toxicology, Daejeon, 34114, Republic of Korea.
Vet Res. 2020 Oct 15;51(1):131. doi: 10.1186/s13567-020-00853-2.
Cefquinome is administered in horses for the treatment of respiratory infection caused by Streptococcus equi subsp. zooepidemicus, and septicemia caused by Escherichia coli. However, there have been no attempts to use cefquinome against Streptococcus equi subsp. equi (S. equi), the causative agent of strangles. Hence the objective of this study was to calculate an optimal dosage of cefquinome against S. equi based on pharmacokinetics and pharmacodynamics integration. Cefquinome (1.0 mg/kg) was administered by intravenous and intramuscular routes to six healthy thoroughbred foals. Serum cefquinome concentrations were determined by high-performance liquid chromatography. The in vitro and ex vivo antibacterial activity were determined from minimum inhibitory concentrations (MIC) and bacterial killing curves. The optimal dosage was calculated from the integration of pharmacokinetic parameters and area under the curve (AUC/MIC) values. Total body clearance and volume of distribution of cefquinome after intravenous administration were 0.06 L/h/kg and 0.09 L/kg, respectively. Following intramuscular administration, a maximum concentration of 0.73 μg/mL at 1.52 h (T) and a systemic bioavailability of 37.45% were observed. The MIC of cefquinome against S. equi was 0.016 μg/mL. The ex vivo AUC/MIC values representing bacteriostatic, and bactericidal activity were 113.11, and 143.14 h, respectively. Whereas the %T > MIC for bactericidal activity was 153.34%. In conclusion, based on AUC/MIC values and pharmacokinetic parameters, cefquinome when administered by intramuscularly at a dosage of 0.53 mg/kg every 24 h, would be effective against infection caused by S. equi in foals. Further studies may be necessary to confirm its therapeutic efficacy in a clinical environment.
头孢喹肟用于治疗马的呼吸道感染由马链球菌兽疫亚种引起，和由大肠杆菌引起的败血症。然而，尚未尝试使用头孢喹肟治疗马链球菌马亚种（S. equi），即马丹毒的病原体。因此，本研究的目的是根据药代动力学和药效学整合计算头孢喹肟对 S. equi 的最佳剂量。头孢喹肟（1.0 毫克/公斤）通过静脉和肌肉途径给予六匹健康的纯种马驹。通过高效液相色谱法测定血清头孢喹肟浓度。通过最低抑菌浓度（MIC）和细菌杀伤曲线测定体外和体外抗菌活性。通过整合药代动力学参数和 AUC/MIC 值来计算最佳剂量。静脉注射后头孢喹肟的总清除率和分布容积分别为 0.06 L/h/kg 和 0.09 L/kg。肌肉注射后，在 1.52 小时（T）时观察到 0.73 μg/mL 的最大浓度和 37.45%的全身生物利用度。头孢喹肟对 S. equi 的 MIC 为 0.016 μg/mL。代表抑菌和杀菌活性的体外 AUC/MIC 值分别为 113.11 和 143.14 h，而杀菌活性的%T>>MIC 为 153.34%。总之，根据 AUC/MIC 值和药代动力学参数，头孢喹肟肌肉注射剂量为 0.53 毫克/公斤，每 24 小时一次，对马驹 S. equi 感染有效。可能需要进一步的研究来确认其在临床环境中的治疗效果。
