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氟甲喹在鳗鲡(欧洲鳗鲡)经血管内、口服和药浴给药后的单剂量药代动力学。

Single-dose pharmacokinetics of flumequine in the eel (Anguilla anguilla) after intravascular, oral and bath administration.

作者信息

Hansen M K, Horsberg T E

机构信息

Department of Pharmacology, Microbiology and Food Hygiene, The Norwegian School of Veterinary Science, Oslo.

出版信息

J Vet Pharmacol Ther. 2000 Jun;23(3):169-74. doi: 10.1046/j.1365-2885.2000.00277.x.

Abstract

Knowledge of the pharmacokinetic properties of drugs to combat bacterial infections in the European eel (Anguilla anguilla) is limited. One antimicrobial agent likely to be effective is flumequine. The aim of this study was to investigate the pharmacokinetic properties of flumequine in European eels in fresh water. Flumequine was administered to eels (Anguilla anguilla) intravenously (i.v.) and orally (p.o.) at a dose of 10 mg/kg body weight, and as a bath treatment at a dose of 10 mg/L water for 2 h. The study was performed in fresh water with a temperature of 23 + 0.3 degrees C, pH 7.15. Identical experimental designs were used. Two additional bath treatments were also performed, one in which the pH in the water was lowered by approximately 1 unit to 6.07 (dose: 10 mg/L) and one at a dose of 40 mg/L for 2 h in a full-scale treatment. Following i.v. administration, the volume of distribution at steady state was 3.4 L/kg. Total body clearance was 0.012 L/h per kg and the elimination half-life (t1/2lambda z) was calculated to be 314 h. Mean residence time was 283 h. Following oral administration, the t1/2lambda z was 208 h. Maximal plasma concentration (Cmax) was 9.3 mg/L, at 7 h after administration (Cmax). The oral bioavailability (F) was calculated to be 85%. Following bath administration in 10 mg/L for 2 h, maximal plasma concentration was 2.1 mg/L, observed immediately after the end of the bath. The 'bioavailability' in eel following a 2-h bath treatment was 19.8%. Reducing the pH in the bath to 6.07 produced a maximal plasma concentration of 5.5 mg/L, observed immediately after the end of the bath. The 'bioavailability' was increased to 41% by the lowering of the pH. A similar effect was observed in a full-scale treatment (1 kg eels/L water). The CO2 produced by the eel lowered the pH and increased 'bioavailability' to 35%.

摘要

关于用于对抗欧洲鳗鲡(Anguilla anguilla)细菌感染的药物的药代动力学特性的知识有限。一种可能有效的抗菌剂是氟甲喹。本研究的目的是调查氟甲喹在淡水中欧洲鳗鲡体内的药代动力学特性。以10 mg/kg体重的剂量对鳗鲡(Anguilla anguilla)进行静脉注射(i.v.)和口服(p.o.),并以10 mg/L水的剂量进行2小时的药浴处理。研究在温度为23 ± 0.3摄氏度、pH值为7.15的淡水中进行。采用相同的实验设计。还进行了另外两种药浴处理,一种是将水中的pH值降低约1个单位至6.07(剂量:10 mg/L),另一种是在全规模处理中以40 mg/L的剂量处理2小时。静脉注射后,稳态分布容积为3.4 L/kg。总体清除率为每千克0.012 L/h,消除半衰期(t1/2lambda z)经计算为314小时。平均驻留时间为283小时。口服给药后,t1/2lambda z为208小时。最大血浆浓度(Cmax)为9.3 mg/L,在给药后7小时达到(Cmax)。口服生物利用度(F)经计算为85%。以10 mg/L进行2小时的药浴处理后,最大血浆浓度为2.1 mg/L,在药浴结束后立即观察到。2小时药浴处理后鳗鲡的“生物利用度”为19.8%。将药浴中的pH值降至6.07后,在药浴结束后立即观察到最大血浆浓度为5.5 mg/L。通过降低pH值,“生物利用度”提高到了41%。在全规模处理(1千克鳗鲡/升水)中观察到了类似的效果。鳗鲡产生的二氧化碳降低了pH值,并将“生物利用度”提高到了35%。

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