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两种温度下经口灌胃后斑点叉尾鮰体内磺胺嘧啶及其代谢物的血浆和组织动力学

The plasma and tissue kinetics of sulfadiazine and its metabolite in Ictalurus punctatus after oral gavage at two temperatures.

作者信息

Xu Ning, Cheng Bo, Yang Yibin, Liu Yongtao, Dong Jing, Yang Qiuhong, Zhou Shun, Song Yi, Ai Xiaohui

机构信息

Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, China.

Hu Bei Province Engineering and Technology Research Center of Aquatic Product Quality and Safety, Wuhan, China.

出版信息

J Vet Pharmacol Ther. 2023 Mar;46(2):125-135. doi: 10.1111/jvp.13114. Epub 2023 Jan 24.

Abstract

A plasma and tissue kinetic study of sulfadiazine (SDZ) and its metabolite, N -acetyl sulfadiazine (ACT-SDZ), was characterized in channel catfish (Ictalurus punctatus) following a single oral dose of 50 mg/kg at 18 and 24°C. Samples were collected at predetermined time points and determined by ultra-performance liquid chromatography. The classical one-compartmental method was used to estimate the pharmacokinetic parameters. Results showed that the changing of temperature was markedly influential on the kinetics of SDZ and ACT-SDZ in plasma and tissues. When the temperature was increased from 18 to 24°C, the elimination half-life (K10_HF) of SDZ was decreased in gill, kidney, and muscle + skin, but increased in liver and plasma. The K10_HF of ACT-SDZ also had a decreased trend in gill, liver, and plasma but had comparable values in kidney and muscle + skin. The absorption half-life (K01_HF), time to peak concentration (T ), and area under concentration-time curve (AUC ) of SDZ and ACT-SDZ all exhibited declined tendencies in plasma and tissues. The apparent volume of distribution (V_F) of SDZ in plasma was increased from 0.53 to 1.48 L/kg, and the apparent systemic total body clearance (Cl_F) was increased from 0.028 to 0.060 L/h/kg. In a word, K01_HF, T , and AUC of SDZ and ACT-SDZ were decreased in plasma and tissues with the increase of temperature, whereas the V_F and Cl_F of SDZ were increased. Meanwhile, we calculated the percentage of time profile of SDZ concentration more than minimum inhibitory concentration to total time (%T > MIC) to guide clinical usage of SDZ. When the dosage interval was 24 h, the values of %T > MIC were all >90% in plasma and most tissues. Therefore, we recommend an oral dose of SDZ at 50 mg/kg once per 24 h at 18-24°C against the fish pathogens with an MIC value of ≤6.4 μg/mL.

摘要

在18°C和24°C条件下,对斑点叉尾鮰单次口服50mg/kg磺胺嘧啶(SDZ)及其代谢产物N - 乙酰磺胺嘧啶(ACT - SDZ)后进行了血浆和组织动力学研究。在预定时间点采集样本,并用超高效液相色谱法进行测定。采用经典的单室模型方法估算药代动力学参数。结果表明,温度变化对血浆和组织中SDZ和ACT - SDZ的动力学有显著影响。当温度从18°C升高到24°C时,鳃、肾脏以及肌肉 + 皮肤中SDZ的消除半衰期(K10_HF)缩短,但肝脏和血浆中的消除半衰期延长。ACT - SDZ的K10_HF在鳃、肝脏和血浆中也有下降趋势,但在肾脏和肌肉 + 皮肤中数值相近。SDZ和ACT - SDZ在血浆和组织中的吸收半衰期(K01_HF)、达峰时间(T)以及浓度 - 时间曲线下面积(AUC)均呈下降趋势。血浆中SDZ的表观分布容积(V_F)从0.53L/kg增加到1.48L/kg,表观全身清除率(Cl_F)从0.028L/h/kg增加到0.060L/h/kg。总之,随着温度升高,血浆和组织中SDZ和ACT - SDZ的K01_HF、T和AUC降低,而SDZ的V_F和Cl_F增加。同时,我们计算了SDZ浓度高于最低抑菌浓度的时间占总时间的百分比(%T > MIC)以指导SDZ的临床应用。当给药间隔为每24小时时,血浆和大多数组织中%T > MIC的值均>90%。因此,我们建议在18 - 24°C条件下,针对最低抑菌浓度≤6.4μg/mL的鱼类病原体,每24小时口服一次50mg/kg的SDZ。

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