Population pharmacokinetic modelling of oxytetracycline in rainbow trout (Oncorhynchus mykiss): Effects of route of administration, temperature and ploidy

IF 3.9 1区农林科学 Q1 FISHERIES

Aquaculture Pub Date : 2025-07-01 DOI:10.1016/j.aquaculture.2025.742917

Alexis Viel , Florine Bachelet , Annaëlle Chailleux , Céline David , Lionel Pineau , Ségolène Calvez , Antoine Rostang

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引用次数: 0

Abstract

The aim of this study was to perform a pharmacokinetic (PK) study of oxytetracycline (OTC) in rainbow trout using different routes of administration and different doses, and to investigate the influence of the bodyweight, the ploidy status (diploid versus triploid) and the water temperature (10 °C versus 16 °C).

A cross-over design was used with 361 trout (median bodyweight: 389 g), each fish receiving OTC intravenously (8–30 mg/kg) and orally (50–150 mg/kg), by gavage or by spontaneous intake via a coating of OTC on the feed to mimic farming practice. Each fish, for each modality, was sampled 3–4 times over a period of 11 days, to establish its individual PK profile. Coated feed and plasma samples were assayed using a sensitive HPLC-MS/MS method. A population PK modelling approach was used to analyse plasma data and estimate key PK parameters and their variability.

A bi-compartmental PK model best described the plasma data. The absolute oral bioavailability appeared to be very low (around 3 %) and the elimination of OTC was slow and strongly influenced by temperature (elimination half-life approximately 79 h at 16 °C versus 113 h at 10 °C). A comparison of spontaneous intake and gavage showed a significant loss of antibiotic due to leaching (about 30 %). Bodyweight and water temperature were the most influential covariates affecting the PK of OTC compared to the effect of ploidy. Pharmacodynamic (PD) studies with OTC against the major trout pathogens are now required to allow a more robust assessment of the expected efficacy thanks to a PK/PD approach.

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土霉素在虹鳟体内的种群药动学模型：给药途径、温度和倍性的影响

本研究的目的是通过不同给药途径和不同剂量对土霉素（OTC）在虹鳟鱼体内的药代动力学（PK）进行研究，并探讨体重、倍体状态（二倍体与三倍体）和水温（10°C与16°C）对土霉素（OTC）的影响。对361条鳟鱼（中位体重：389 g）进行交叉试验，每条鱼分别静脉注射OTC （8-30 mg/kg）和口服OTC (50-150 mg/kg)，通过灌胃或通过在饲料上涂覆OTC来模拟养殖实践。在11天的时间内，对每种模式的每条鱼取样3-4次，以建立其个体PK剖面。包膜饲料和血浆样品采用高效液相色谱-质谱联用（HPLC-MS/MS）检测。种群PK建模方法用于分析血浆数据，估计关键PK参数及其变异性。双区室PK模型最好地描述了等离子体数据。绝对口服生物利用度似乎非常低（约3%），OTC的消除缓慢且受温度的强烈影响（16℃时的消除半衰期约为79 h，而10℃时为113 h）。自发摄入和灌胃的比较显示，抗生素因浸出而大量流失（约30%）。相对于倍性的影响，体重和水温是影响OTC PK的最大协变量。由于采用PK/PD方法，现在需要进行OTC对主要鳟鱼病原体的药效学（PD）研究，以便对预期疗效进行更可靠的评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Aquaculture 农林科学-海洋与淡水生物学

CiteScore

8.60

自引率

17.80%

发文量

1246

审稿时长

56 days

期刊介绍： Aquaculture is an international journal for the exploration, improvement and management of all freshwater and marine food resources. It publishes novel and innovative research of world-wide interest on farming of aquatic organisms, which includes finfish, mollusks, crustaceans and aquatic plants for human consumption. Research on ornamentals is not a focus of the Journal. Aquaculture only publishes papers with a clear relevance to improving aquaculture practices or a potential application.