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三种不同剂量肌肉注射后,长效土霉素制剂在淡水鳄鱼体内的药代动力学

Pharmacokinetics of a Long-Acting Formulation of Oxytetracycline in Freshwater Crocodiles () after Intramuscular Administration at Three Different Dosages.

作者信息

Poapolathep Saranya, Klangkaew Narumol, Phaochoosak Napasorn, Wongwaipairoj Tara, Giorgi Mario, Chaiyabutr Narongsak, Trott Darren J, Poapolathep Amnart

机构信息

Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand.

Wongveerakit Crocodile Farm, Bo Phloi, Kanjanaburi 71160, Thailand.

出版信息

Animals (Basel). 2020 Jul 27;10(8):1281. doi: 10.3390/ani10081281.

Abstract

To date, the necessary pharmacokinetic information has been limited to establish suitable therapeutic plans for freshwater crocodiles. Therefore, this study was conducted to evaluate the pharmacokinetic profile of the oxytetracycline long-acting formulation (OTC-LA) in the freshwater crocodile, , following a single intramuscular (i.m.) administration at three different dosages of 5, 10 and 20 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 216 h after i.m. administration at the three different dosages. The plasma concentrations of OTC were measured using a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. The C (± SD) values of OTC were 2.15 ± 0.51 µg/mL, 7.68 ± 1.08 µg/mL and 17.08 ± 2.09 µg/mL at doses of 5, 10 and 20 mg/kg b.w., respectively. The elimination half-life values were 33.59 ± 2.51 h, 38.42 ± 5.47 h and 38.04 ± 1.98 h at dosages of 5, 10 and 20 mg/kg b.w., respectively. Based on the pharmacokinetic data, the pharmacokinetic/pharmacodynamic (PK/PD) index, the susceptibility break-point and plasma protein binding, a dosage once every two weeks of 10 mg/kg b.w. OTC intramuscularly might be suitable for initiating the treatment of susceptible bacterial infections in freshwater crocodiles. However, further PK/PD studies are warranted to confirm whether the dose rates used in this study can produce longer-term antimicrobial success for diseases caused by susceptible bacteria in freshwater crocodiles.

摘要

迄今为止,为淡水鳄鱼制定合适的治疗方案所需的药代动力学信息有限。因此,本研究旨在评估长效土霉素制剂(OTC-LA)在淡水鳄鱼体内的药代动力学特征,在三种不同剂量(5、10和20毫克/千克体重)下进行单次肌肉注射后进行研究。在三种不同剂量下肌肉注射后长达216小时的指定时间采集血样。使用经过验证的液相色谱串联质谱(LC-MS/MS)方法测量血浆中土霉素的浓度。在5、10和20毫克/千克体重剂量下,土霉素的C(±标准差)值分别为2.15±0.51微克/毫升、7.68±1.08微克/毫升和17.08±2.09微克/毫升。在5、10和20毫克/千克体重剂量下,消除半衰期值分别为33.59±2.51小时、38.42±5.47小时和38.04±1.98小时。根据药代动力学数据、药代动力学/药效学(PK/PD)指数、药敏断点和血浆蛋白结合情况,每两周一次肌肉注射10毫克/千克体重的土霉素剂量可能适合用于开始治疗淡水鳄鱼的敏感细菌感染。然而,需要进一步的PK/PD研究来确认本研究中使用的剂量率是否能对淡水鳄鱼中由敏感细菌引起的疾病产生长期抗菌效果。

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