Corum Orhan, Altan Feray, Yildiz Ramazan, Ider Merve, Ok Mahmut, Uney Kamil
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Kastamonu, Kastamonu, Turkey.
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Dicle, Diyarbakir, Turkey.
J Vet Pharmacol Ther. 2019 Nov;42(6):624-631. doi: 10.1111/jvp.12787. Epub 2019 Jun 12.
The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty-four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR-IV (10 mg/kg, IV), ENR-IM (10 mg/kg, IM), DNX-IV (8 mg/kg, IV), and DNX-IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high-pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half-life (t ) 11.16 and 17.47 hr, area under the plasma concentration-time curve (AUC ) 139.75 and 38.90 hrµg/ml, and volume of distribution at steady-state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr kg , respectively. The PK parameters of ENR and DNX following IM injection were t 21.10 and 28.41 hr, AUC 164.34 and 48.32 hrµg/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC /AUC ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC /minimum inhibitory concentration (MIC) and maximum concentration (C )/MIC ratios for susceptible bacteria, with the MIC of 0.5 and 0.03 μg/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.
本研究的目的是确定恩诺沙星(ENR)和达氟沙星(DNX)在早产犊牛静脉注射(IV)和肌肉注射(IM)后的药代动力学/药效学。该研究对24头通过病史和一般临床检查确定为早产的犊牛进行。根据平行药代动力学(PK)设计,早产犊牛被随机分为四组(每组6头早产犊牛),如下:ENR-IV(10mg/kg,静脉注射)、ENR-IM(10mg/kg,肌肉注射)、DNX-IV(8mg/kg,静脉注射)和DNX-IM(8mg/kg,肌肉注射)。采集血浆样本,通过带紫外检测器的高压液相色谱法测定受试药物,并采用非房室方法进行分析。ENR和DNX静脉注射后的平均PK参数如下:消除半衰期(t)分别为11.16和17.47小时,血浆浓度-时间曲线下面积(AUC)分别为139.75和38.90小时μg/ml,稳态分布容积分别为1.06和4.45L/kg。ENR和DNX的总体清除率分别为0.07和0.18L·小时-1·kg-1。ENR和DNX肌肉注射后的PK参数分别为t 21.10和28.41小时,AUC分别为164.34和48.32小时μg/ml。ENR和DNX的生物利用度(F)分别确定为118%和124%。在早产犊牛中,静脉注射和肌肉注射后的平均AUC0-24/AUC0-∞比值分别为0.20和0.16。结果表明,ENR(10mg/kg)和DNX(8mg/kg)静脉注射和肌肉注射后产生的血浆浓度足以满足AUC/最低抑菌浓度(MIC)和最大浓度(Cmax)/MIC比值对敏感细菌的要求,其MIC分别为0.5和0.03μg/ml。这些发现可能有助于规划ENR和DNX的给药方案,但需要在自然感染的早产犊牛中进一步研究。