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地塞米松对哺乳期绵羊血浆及乳汁中达氟沙星处置动力学的影响

Influence of Dexamethasone on the Plasma and Milk Disposition Kinetics of Danofloxacin in Lactating Sheep.

作者信息

Uney Kamil, Yildiz Ramazan, Durna Corum Duygu, Ider Merve, Corum Orhan

机构信息

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, Konya 42031, Türkiye.

Department of Internal Medicine, Faculty of Veterinary Medicine, University of Burdur Mehmet Akif Ersoy, Burdur 15030, Türkiye.

出版信息

Vet Sci. 2025 Mar 1;12(3):210. doi: 10.3390/vetsci12030210.

DOI:10.3390/vetsci12030210
PMID:40266936
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11946273/
Abstract

This study planned to evaluate the impact of low (0.1 mg/kg) and high (1 mg/kg) doses of dexamethasone on the plasma and milk distribution of danofloxacin (6 mg/kg) in sheep after intravenous administration. Utilizing a crossover pharmacokinetic design, the research was conducted on six lactating ewes, with blood and milk samples collected at 18 predetermined time points over a 48-h period. Danofloxacin analysis from plasma and milk samples was performed by high-performance liquid chromatography. The pharmacokinetic data were derived using non-compartmental analysis. Plasma t, AUC, Cl, and V values of danofloxacin were found to be 5.20 h, 9.26 hµg/mL, 0.65 L/h/kg, and 4.23 L/kg, respectively. The administration of both low and high doses of dexamethasone did not result in any changes in the plasma pharmacokinetics of danofloxacin. Milk t, AUC, and C values of danofloxacin were 4.30 h, 99.52 hµg/mL, and 20.61 µg/mL, respectively. Dexamethasone administration resulted in prolonged milk t, with high-dose dexamethasone significantly enhancing both the milk AUC and C of danofloxacin. The AUC/AUC ratio of danofloxacin was 10.75 and was further increased with dexamethasone treatment. These results highlight the necessity for careful evaluation of drug interactions in lactating sheep to ensure both efficacy and safety, as well as the need for further research to establish guidelines for concurrent administration of dexamethasone and danofloxacin.

摘要

本研究计划评估低剂量(0.1毫克/千克)和高剂量(1毫克/千克)地塞米松对静脉注射达氟沙星(6毫克/千克)后在绵羊体内血浆和乳汁分布的影响。采用交叉药代动力学设计,对6只泌乳母羊进行研究,在48小时内的18个预定时间点采集血液和乳汁样本。通过高效液相色谱法对血浆和乳汁样本中的达氟沙星进行分析。药代动力学数据采用非房室分析得出。达氟沙星的血浆t、AUC、Cl和V值分别为5.20小时、9.26小时·微克/毫升、0.65升/小时/千克和4.23升/千克。低剂量和高剂量地塞米松的给药均未导致达氟沙星血浆药代动力学发生任何变化。达氟沙星的乳汁t、AUC和C值分别为4.30小时、99.52小时·微克/毫升和20.61微克/毫升。地塞米松给药导致乳汁t延长,高剂量地塞米松显著提高了达氟沙星的乳汁AUC和C。达氟沙星的AUC/AUC比值为10.75,地塞米松治疗后进一步升高。这些结果凸显了在泌乳绵羊中仔细评估药物相互作用以确保疗效和安全性的必要性,以及进一步研究以建立地塞米松和达氟沙星联合给药指南的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5057/11946273/9e39cc0770b6/vetsci-12-00210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5057/11946273/4f0e3905a818/vetsci-12-00210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5057/11946273/9e39cc0770b6/vetsci-12-00210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5057/11946273/4f0e3905a818/vetsci-12-00210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5057/11946273/9e39cc0770b6/vetsci-12-00210-g002.jpg

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J Vet Pharmacol Ther. 2022 Nov;45(6):570-577. doi: 10.1111/jvp.13086. Epub 2022 Jul 16.
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