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恩诺沙星单次口服给药在黄河鲤体内的药代动力学及组织分布()

Pharmacokinetics and Tissue Distribution of Enrofloxacin Following Single Oral Administration in Yellow River Carp ().

作者信息

Yang Fan, Zhang Chao-Shuo, Duan Ming-Hui, Wang Han, Song Zhe-Wen, Shao Hao-Tian, Ma Kai-Li, Yang Fang

机构信息

Department of Veterinary Pharmacology, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China.

出版信息

Front Vet Sci. 2022 Feb 4;9:822032. doi: 10.3389/fvets.2022.822032. eCollection 2022.

Abstract

The pharmacokinetics and tissue distribution of enrofloxacin were determined in Yellow River carp () reared at 20°C after single oral administration of enrofloxacin at 10 mg·kg body weight (BW). Plasma, bile, and different tissue samples, including liver, kidney, gill, gut, and skin-muscle, were collected at predetermined times points. An HPLC method was developed to simultaneously determine the concentrations of enrofloxacin and its metabolite, ciprofloxacin. However, ciprofloxacin was only detectable in some liver samples with trace levels. Then the average enrofloxacin concentrations vs. time data were subjected to a non-compartmental analysis using WinNonLin 5.2 software. Multiple peaking profiles were observed in all enrofloxacin concentration-time curves. The peak concentration (C) values were observed as 0.79, 1.01, 2.09, 2.85, 4.34, 10.78, and 13.07 μg·ml (or g) in plasma, skin-muscle, gill, kidney, liver, bile, and gut, respectively, and the corresponding time to reach peak concentration (T) was 8, 8, 1, 8, 1, 72, and 4 h, respectively. The values of elimination half-life (T ) of enrofloxacin in different tissues was in the following order: gill (291.13 h) > liver (222.29 h) > kidney (157.22 h) > plasma (129.44 h) > gut (91.47 h) > skin-muscle (87.77 h) > bile (86.22 h). The present results showed that enrofloxacin had a wide distribution in different tissues, however slow absorption and elimination in Yellow River carp. Additionally, enrofloxacin exhibited large distribution in bile, indicating that bile excretion might be the primary elimination route of enrofloxacin in Yellow River carp. A withdrawal period was calculated as 379.2 °C-day for single oral dosing of enrofloxacin at 10 mg/kg BW. Based on the calculated PK/PD indices of AUC/MIC or C/MIC, the current enrofloxacin dosing regimen might have a positive therapeutic effect on the infection of , or . However, the depletion study following multiple oral doses should be carried out in Yellow River carp reared at lower temperatures, and the withdrawal period should also be further calculated.

摘要

在20°C水温下饲养的黄河鲤( )中,单次口服10 mg·kg体重(BW)恩诺沙星后,测定了其药代动力学和组织分布情况。在预定时间点采集血浆、胆汁以及包括肝脏、肾脏、鳃、肠道和皮肤肌肉在内的不同组织样本。开发了一种高效液相色谱法,用于同时测定恩诺沙星及其代谢物环丙沙星的浓度。然而,环丙沙星仅在部分肝脏样本中可检测到,且含量极低。然后,使用WinNonLin 5.2软件对恩诺沙星的平均浓度与时间数据进行非房室分析。在所有恩诺沙星浓度 - 时间曲线中均观察到多峰现象。血浆、皮肤肌肉、鳃、肾脏、肝脏、胆汁和肠道中恩诺沙星的峰浓度(C)值分别为0.79、1.01、2.09、2.85、4.34、10.78和13.07 μg·ml(或g),相应的达峰时间(T)分别为8、8、1、8、1、72和4小时。恩诺沙星在不同组织中的消除半衰期(T )值顺序如下:鳃(291.13小时)>肝脏(222.29小时)>肾脏(157.22小时)>血浆(129.44小时)>肠道(91.47小时)>皮肤肌肉(87.77小时)>胆汁(86.22小时)。目前的结果表明,恩诺沙星在黄河鲤的不同组织中分布广泛,但吸收和消除缓慢。此外,恩诺沙星在胆汁中分布量大,表明胆汁排泄可能是恩诺沙星在黄河鲤中的主要消除途径。计算得出,单次口服10 mg/kg BW恩诺沙星的休药期为379.2 °C - 天。基于计算得到的AUC/MIC或C/MIC的药代动力学/药效学指标,目前的恩诺沙星给药方案可能对 、 或 的感染具有积极的治疗效果。然而,应在较低水温下饲养的黄河鲤中进行多次口服给药后的药物残留研究,并且还应进一步计算休药期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/8855120/d49544ad80c4/fvets-09-822032-g0001.jpg

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