河口鳄鱼(Crocodylus porosus)肌肉注射后的药物代谢分布。

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Journal of veterinary pharmacology and therapeutics Pub Date : 2023-06-28 DOI:10.1111/jvp.13400
Mona Yalong, Saranya Poapolathep, Mario Giorgi, Kraisiri Khidkhan, Narumol Klangkaew, Napasorn Phaochoosak, Narongsak Chaiyabutr, Tara Wongwaipairoj, Amnart Poapolathep
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引用次数: 0

摘要

迄今为止,有关氟喹诺酮类药物在河口鳄鱼(Crocodylus porosus)体内的药代动力学的报道仅涉及恩诺沙星,而未涉及马勃沙星(MBF),后者是一种仅用于兽医的广谱抗生素。本研究调查了河口鳄肌肉注射两种不同剂量(2 毫克和 4 毫克/千克体重)的 MBF 的药代动力学,并估算了药代动力学/药效学(PK/PD)替代参数,以优化剂量方案。根据平行研究设计,采用随机程序将 10 只经过治疗的河口鳄鱼分为两组(n = 5)。使用液液萃取法对 MBF 血浆样本进行净化,并使用经过验证的荧光检测高效液相色谱法进行分析。采用非室方法拟合了每条鳄鱼血浆中 MBF 浓度与时间的关系曲线。两组鳄鱼的血浆中 MBF 浓度在 168 小时内均可定量。甲基溴论坛的消除半衰期较长(2 毫克/千克和 4 毫克/千克的消除半衰期分别为 33.99 和 39.28 小时),各组之间没有显著差异。MBF 的平均血浆蛋白结合率为 30.85%。根据代用 PK/PD 参数(AUC0-24 与 MIC 比值 >100-125),2 毫克/公斤和 4 毫克/公斤的剂量对 MIC 值分别低于 0.125 微克/毫升和 0.35 微克/毫升的细菌有效。
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Pharmacokinetic disposition of marbofloxacin after intramuscular administration in estuarine crocodiles (Crocodylus porosus)

To date, the pharmacokinetics of fluoroquinolones in estuarine crocodiles (Crocodylus porosus) have been reported for enrofloxacin but not for marbofloxacin (MBF), which is a broad-spectrum antibiotic used only in veterinary medicine. This study investigated the pharmacokinetics of MBF after intramuscular administration at two difference dosages (2 and 4 mg/kg body weight) in estuarine crocodiles and estimated pharmacokinetic/pharmacodynamic (PK/PD) surrogate parameters for the optimization of dosage regimens. Ten treated estuarine crocodiles were divided into two groups (n = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at assigned times up to 168 h. MBF plasma samples were cleaned up using liquid–liquid extraction and analyzed using a validated high-performance liquid chromatography method with fluorescence detection. A non-compartment approach was used to fit the plasma concentration of MBF vs time curve for each crocodile. The plasma concentrations of MBF were quantifiable for up to 168 h in both groups. The elimination half-life values of MBF were long (33.99 and 39.28 h for 2 and 4 mg/kg, respectively) with no significant differences between the groups. The average plasma protein binding of MBF was 30.85%. According to the surrogated PK/PD parameter (AUC0–24-to-MIC ratio >100–125), the 2 and 4 mg/kg dosing rates should be effective for bacteria with MIC values lower than 0.125 μg/mL and 0.35 μg/mL, respectively.

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来源期刊
CiteScore
3.10
自引率
15.40%
发文量
69
审稿时长
8-16 weeks
期刊介绍: The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.
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