ICAR-Directorate of Coldwater Fisheries Research (ICAR-DCFR), Anusandhan Bhavan, Industrial Area, Bhimtal, Nainital, 263 136, Uttarakhand, India.
ICAR- Central Institute of Brackishwater Aquaculture (ICAR-CIBA), Raja Annamalai Puram, Chennai, 600028, Tamil Nadu, India.
Sci Rep. 2024 Oct 1;14(1):22752. doi: 10.1038/s41598-024-73921-8.
The aim of the experiment was to investigate the pharmacokinetics of oxytetracycline dihydrate after a single oral administration of 80 mg kg day in rainbow trout and assess its biosafety at concentration of 80, 240, 400, and 800 mg kg day over 30 days, focusing on various aspects such as effective feed consumption, physiological responses, drug tolerance, and detection of low drug concentrations in rainbow trout. The pharmacokinetics study spanned a duration of 5 days, while the assessment of biosafety extended for a 30-day safety margin, followed by a subsequent 10-day residual analysis. Pharmacokinetic analysis revealed slow absorption with low-rate constant in tissues. Absorption rates vary among tissues, with the gill showing the highest rate (0.011 h) and plasma exhibiting the slowest (0.0002 h). According to pharmacokinetic analysis, the highest concentration, C (µg kg) was observed in the kidney (9380 µg kg) and gill (8710 µg kg), and lowest in muscle (2460 µg kg). The time (T) to reach peak concentration (C) varied among tissues, ranging from 3 h in the gill to 32 h in the muscle, with 24 h in plasma, 32 h in the kidney, and 16 h in both the liver and skin. The liver and kidney had the highest area under the concentration-time curve (AUC), indicating widespread drug distribution. Prolonged elimination occurred at varying rates across tissues, with the gill showing the highest rate. The study found that OTC concentrations exceeded the LOD and LOQ values. Biosafety evaluation showed effective feed consumption, physiological responses, and low drug concentrations in muscle at the recommended dosage of 80 mg kg fish day.
本实验旨在研究单剂量 80mg/kg 体重口服二水氧四环素后，虹鳟体内的药代动力学，并评估其在 80、240、400 和 800mg/kg 体重浓度下 30 天的生物安全性，重点关注有效摄食量、生理反应、药物耐受性以及虹鳟肌肉中低药物浓度的检测。药代动力学研究持续 5 天，而生物安全性评估则持续 30 天的安全边际，随后进行 10 天的残留分析。药代动力学分析表明，组织吸收缓慢，速率常数较低。吸收速率在不同组织之间存在差异，其中鳃的吸收速率最高（0.011h），血浆的吸收速率最慢（0.0002h）。根据药代动力学分析，在肾脏（9380µg/kg）和鳃（8710µg/kg）中观察到最高浓度 C（µg/kg），而在肌肉中则最低（2460µg/kg）。达到峰值浓度 C 的时间（T）在组织之间有所不同，从鳃的 3h 到肌肉的 32h，血浆为 24h，肾脏为 32h，肝脏和皮肤为 16h。肝脏和肾脏的浓度-时间曲线下面积（AUC）最高，表明药物广泛分布。在不同组织中，药物消除速度不同，其中鳃的消除速度最快。研究发现，OTC 浓度超过了 LOD 和 LOQ 值。生物安全性评估表明，在推荐剂量 80mg/kg 体重鱼日时，有效摄食量、生理反应和肌肉中的低药物浓度。
