Robert Goggs, Sarah Robbins, Julie Menard, Jamie Selman, Jeff Beverly, Sydney Kraus-Mallet, Mark G Papich
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引用次数: 0
摘要
氟喹诺酮类药物,特别是恩诺沙星,在小动物急诊和重症监护实践中经常用于治疗危及生命的细菌感染。达到治疗性血浆浓度对于有效治疗至关重要,而浓度不足则会导致肠杆菌和铜绿假单胞菌产生耐药性。我们对19只危重犬进行了前瞻性观察研究,以评估恩诺沙星及其活性代谢物环丙沙星在给予标准剂量(10 mg/kg IV q24 h)后的药代动力学(PK)。使用液相色谱-质谱法测量多个时间点的血浆浓度,并进行PK建模以确定最适合的室室模型。2室模型最好地描述了恩诺沙星的PK。狗之间的PK参数有相当大的差异,可能是由于已知的危重疾病中药物剂量的挑战。在健康犬中,恩诺沙星转化为环丙沙星的百分比低于先前的报道。药效学分析表明,对危重犬给予10mg /kg IV / 24h的恩诺沙星可能会有效治疗易感细菌和易感剂量依赖细菌的感染,并且达到的浓度可能足以降低AMR发生的风险。
Routine Doses of Enrofloxacin Achieve Pharmacodynamic Target Likely to Treat Susceptible and Susceptible Dose-Dependent Bacterial Infections in Critically Ill Dogs.
The fluoroquinolones, particularly enrofloxacin, are frequently used to treat life-threatening bacterial infections in small animal emergency and critical care practice. Achieving therapeutic plasma concentrations is essential for effective treatment, whereas inadequate concentrations select for resistance among Enterobacterales and Pseudomonas aeruginosa. We conducted a prospective observational study in 19 critically ill dogs to evaluate the pharmacokinetics (PK) of enrofloxacin and its active metabolite ciprofloxacin after administration of a standardized dosage (10 mg/kg IV q24 h). Plasma concentrations were measured at multiple time points using liquid chromatography-mass spectrometry, and PK modeling was performed to determine best-fit compartmental models. A 2-compartment model best described enrofloxacin PK. There was considerable between-dog variation in PK parameters, likely due to known challenges of drug dosing in critical illness. The percentage conversion of enrofloxacin to ciprofloxacin was lower than has previously been reported in healthy dogs. Pharmacodynamic analyses suggest that enrofloxacin administered at 10 mg/kg IV q24 h to critically ill dogs will likely result in effective treatment of infections by susceptible and susceptible dose-dependent bacteria, and achieved concentrations may be sufficient to reduce the risk of AMR development.
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.