Department of Epidemiology and Preventive Veterinary Medicine, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Science University, Ludhiana 141004, Punjab, India.
Vet J. 2010 May;184(2):219-29. doi: 10.1016/j.tvjl.2009.02.009. Epub 2009 Mar 18.
In a four-period cross-over study, the fluoroquinolone antibacterial drug marbofloxacin (MB) was administered to goats intramuscularly (IM) at a dose rate of 2 mg/kg, both alone and in combination with the non-steroidal anti-inflammatory drug tolfenamic acid (TA), also administered IM at a dose rate of 2 mg/kg. Using a tissue cage model of inflammation, based on the irritant actions of carrageenan, the pharmacokinetics (PK) of MB and MB in combination with TA were determined. MB mean values of area under concentration-time curve (AUC) were similar for serum (5.60 microg h/mL), inflamed tissue cage fluid (exudate; 5.32 microg h/mL) and non-inflamed tissue cage fluid (transudate; 4.82 microg h/mL). Values of mean residence time (MRT) of MB in exudate (15.5 h) and transudate (15.8 h) differed significantly from serum MRT (4.23 h). Co-administration of TA did not affect the PK profile of MB. The pharmacodynamics of MB were investigated using a caprine strain of Mannheimia haemolytica. Integration of PK data with ex vivo bacterial time-kill curve data for serum, exudate and transudate provided AUC(24h)/minimum inhibitory concentration (MIC) ratios of 160, 133 and 121 h, respectively, for the strain of organism used. Modelling of the ex vivo time-kill data to the sigmoid E(max) equation provided AUC(24h)/MIC values required for bacteriostatic and bactericidal actions of MB and for virtual eradication of the organism of 27.6, 96.2 and 147.3 h, respectively. Corresponding values for MB+TA were 20.5, 66.5 and 103.0 h. These data were used to predict once daily dosage schedules of MB for subsequent clinical evaluation.
在一项四周期交叉研究中，氟喹诺酮类抗菌药物马波沙星（MB）以 2mg/kg 的肌内（IM）剂量单独给药，以及与非甾体抗炎药托芬那酸（TA）联合给药，也以 2mg/kg 的肌内剂量给药。使用基于卡拉胶的刺激性作用的炎症组织笼模型，确定 MB 和 MB 与 TA 联合使用的药代动力学（PK）。MB 的血清（5.60μg h/mL）、炎症组织笼液（渗出液；5.32μg h/mL）和非炎症组织笼液（漏出液；4.82μg h/mL）的 AUC 值的平均值相似。MB 在渗出液（15.5h）和漏出液（15.8h）中的平均驻留时间（MRT）值与血清 MRT（4.23h）显著不同。TA 的共同给药不影响 MB 的 PK 特征。使用曼海姆氏嗜血杆菌的山羊株研究 MB 的药效动力学。将 PK 数据与血清、渗出液和漏出液的体外细菌时间杀菌曲线数据整合，为所用菌株提供了 AUC(24h)/最低抑菌浓度（MIC）比值分别为 160、133 和 121 h。对体外时间杀菌数据进行 sigmoid E(max)方程的建模，为 MB 的抑菌和杀菌作用以及对生物体的虚拟根除提供了 AUC(24h)/MIC 值，分别为 27.6、96.2 和 147.3 h。MB+TA 的相应值分别为 20.5、66.5 和 103.0 h。这些数据用于预测 MB 的每日一次剂量方案，以便随后进行临床评估。
