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生长雄性火鸡中恩诺沙星剂量的异速生长优化:改善体内暴露的实证证据

Allometric Optimization of Enrofloxacin Dosage in Growing Male Turkeys: Empirical Evidence for Improved Internal Exposure.

作者信息

Poźniak Błażej, Tikhomirov Marta, Motykiewicz-Pers Karolina, Bobrek Kamila, Świtała Marcin

机构信息

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, ul. Norwida 31, 50-375 Wrocław, Poland.

Department of Epizootiology and Clinic of Birds and Exotic Animals, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, pl. Grunwaldzki 45, 50-366 Wrocław, Poland.

出版信息

Antibiotics (Basel). 2020 Dec 18;9(12):925. doi: 10.3390/antibiotics9120925.

Abstract

Rapid weight gain in turkeys causes a major change in the pharmacokinetics of drugs, leading to age-dependent variability in the internal exposure and, possibly, treatment failure and/or selection for antimicrobial resistance in young individuals. The aim of the study was to investigate whether a non-linear dosing protocol that accounts for the previously established allometric relation between enrofloxacin clearance and body weight (BW) may optimize the internal exposure to enrofloxacin in growing male turkeys. Enrofloxacin was administered four times, between the age of 5 and 16.5 weeks, when the turkeys' BW increased from 1.47 to 14.92 kg. Enrofloxacin was given intravenously (i.v.) or orally at the dose calculated as follows: Dose = 30 × BW. After i.v. administration, the internal exposure to the drug-quantified as the area under the concentration-time curve (AUC)-was showing little age-related variation. The coefficient of variation (CV) for AUC in all individuals (15.7%) was only slightly higher than within the age groups (5.4-13.7%). After oral drug administration, CV for AUC in all individuals (22.1%) was similar as within the age groups (8.7-32.2%). These results show that intra-species allometric scaling may be efficiently implemented in the non-linear approach to enrofloxacin dosage in turkeys in order to obtain a precise internal exposure for the optimal antimicrobial effect.

摘要

火鸡体重快速增加会导致药物药代动力学发生重大变化,从而导致体内暴露呈现年龄依赖性变异性,并可能导致幼龄个体治疗失败和/或产生抗菌药物耐药性。本研究的目的是调查一种非线性给药方案,该方案考虑了先前确定的恩诺沙星清除率与体重(BW)之间的异速生长关系,是否可以优化生长中的雄性火鸡体内恩诺沙星的暴露量。在5至16.5周龄期间,当火鸡体重从1.47千克增加到14.92千克时,恩诺沙星给药四次。恩诺沙星通过静脉注射(i.v.)或口服给药,剂量计算如下:剂量=30×BW。静脉注射给药后,药物的体内暴露量(以浓度-时间曲线下面积(AUC)量化)显示出与年龄相关的微小变化。所有个体AUC的变异系数(CV)(15.7%)仅略高于各年龄组内的变异系数(5.4-13.7%)。口服给药后,所有个体AUC的CV(22.1%)与各年龄组内的CV(8.7-32.2%)相似。这些结果表明,种内异速生长标度可以有效地应用于火鸡恩诺沙星剂量的非线性方法中,以便获得精确的体内暴露量以实现最佳抗菌效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1cb/7766516/6cc0f9d1023d/antibiotics-09-00925-g001.jpg

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