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静脉注射达氟沙星在牛体内的临床药代动力学

Clinical pharmacokinetics of parenterally administered danofloxacin in cattle.

作者信息

Giles C J, Magonigle R A, Grimshaw W T, Tanner A C, Risk J E, Lynch M J, Rice J R

机构信息

Pfizer Central Research, Sandwich, Kent, UK.

出版信息

J Vet Pharmacol Ther. 1991 Dec;14(4):400-10. doi: 10.1111/j.1365-2885.1991.tb00854.x.

Abstract

Danofloxacin is a new fluoroquinolone antibacterial, developed specifically for veterinary use. Its in vitro activity and pharmacokinetic properties have been investigated to assess its potential for use in the therapy of respiratory disease in cattle. The minimum inhibitory concentration of danofloxacin against 90% (MIC90) of contemporary European and North American field isolates of Pasteurella haemolytica, Pasteurella multocida and Haemophilus somnus, the most important bacterial respiratory pathogens of cattle, was 0.125 micrograms/ml. The plasma and lung kinetics of danofloxacin following parenteral administration of 1.25 mg/kg were evaluated in two studies. Danofloxacin was rapidly absorbed following intramuscular and subcutaneous injection and bioavailability was virtually complete (101% and 94% respectively). Plasma concentration profiles of danofloxacin were similar for intramuscular and subcutaneous routes with no significant differences in the area under the plasma concentration-time curves (AUC) following one, three or five consecutive daily doses, although slightly higher peak plasma concentrations were achieved by the intramuscular route. Following intramuscular administration, the mean peak lung concentration of danofloxacin was 4.1 times greater than that of plasma. Similarly, the AUC for lung tissue was 3.7 times greater than that for plasma. These data indicate that danofloxacin should be particularly appropriate for the therapy of bacterial respiratory disease in cattle.

摘要

达氟沙星是一种新型氟喹诺酮类抗菌药,专为兽用而研发。已对其体外活性和药代动力学特性进行了研究,以评估其用于治疗牛呼吸道疾病的潜力。达氟沙星对当代欧洲和北美牛的最重要细菌性呼吸道病原体溶血巴斯德菌、多杀巴斯德菌和睡眠嗜血杆菌90%菌株的最低抑菌浓度(MIC90)为0.125微克/毫升。在两项研究中评估了1.25毫克/千克剂量的达氟沙星经肠胃外给药后的血浆和肺部动力学。肌肉注射和皮下注射后,达氟沙星吸收迅速,生物利用度几乎达到完全(分别为101%和94%)。肌肉注射和皮下给药途径的达氟沙星血浆浓度曲线相似,连续每日给药一次、三次或五次后,血浆浓度-时间曲线下面积(AUC)无显著差异,不过肌肉注射途径的血浆峰浓度略高。肌肉注射后,达氟沙星在肺部的平均峰浓度比血浆高4.1倍。同样,肺组织的AUC比血浆高3.7倍。这些数据表明,达氟沙星应特别适用于治疗牛的细菌性呼吸道疾病。

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