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静脉注射和口服给药后肉鸡体内T-2毒素及其主要代谢产物的毒代动力学

Toxicokinetics of T-2 toxin and its major metabolites in broiler chickens after intravenous and oral administration.

作者信息

Sun Y X, Yao X, Shi S N, Zhang G J, Xu L X, Liu Y J, Fang B H

机构信息

National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

出版信息

J Vet Pharmacol Ther. 2015 Feb;38(1):80-5. doi: 10.1111/jvp.12142. Epub 2014 Jul 31.

Abstract

T-2 toxin, one of the most toxic trichothecene mycotoxins, causes economic losses in animal production. Little information is available on the toxicokinetic parameters of T-2 toxin and its major metabolites (i.e., HT-2 toxin and T-2 triol) in broiler chickens. In this study, toxicokinetics of T-2 toxin and its major metabolites were evaluated in broiler chickens after a single intravenous (0.5 mg/kg b.w.) and multiple oral administrations (2.0 mg/kg b.w., every 12 h for 2 days). Plasma concentration profiles of T-2 toxin and its metabolites were analyzed by a noncompartmental model method. Following intravenous administration, the terminal elimination half-lives (t(1/2λz)) of T-2 toxin, HT-2 toxin, and T-2 triol were 17.33 ± 1.07 min, 33.62 ± 3.08 min, and 9.60 ± 0.50 min, respectively. Following multiple oral administrations, no plasma levels above the limit of quantification were observed for HT-2 toxin. The t(1/2λz) of T-2 toxin and T-2 triol was 23.40 ± 2.94 min and 87.60 ± 29.40 min, respectively. Peak plasma concentrations (Cmax ) of 53.10 ± 10.42 ng/mL (T-2 toxin) and 47.64 ± 9.19 ng/mL (T-2 triol) were observed at Tmax of 13.20 ± 4.80 min and 38.40 ± 15.00 min, respectively. T-2 toxin had a low absolute oral bioavailability (17.07%). Results showed that the T-2 toxin was rapidly absorbed and most of the T-2 toxin was extensively transformed to metabolites in broiler chickens.

摘要

T-2毒素是毒性最强的单端孢霉烯族霉菌毒素之一,会给动物生产带来经济损失。关于T-2毒素及其主要代谢产物(即HT-2毒素和T-2三醇)在肉鸡体内的毒代动力学参数,目前所知甚少。在本研究中,对肉鸡单次静脉注射(0.5毫克/千克体重)和多次口服给药(2.0毫克/千克体重,每12小时一次,共2天)后T-2毒素及其主要代谢产物的毒代动力学进行了评估。采用非房室模型方法分析了T-2毒素及其代谢产物的血浆浓度曲线。静脉注射后,T-2毒素、HT-2毒素和T-2三醇的末端消除半衰期(t(1/2λz))分别为17.33±1.07分钟、33.62±3.08分钟和9.60±0.50分钟。多次口服给药后,未观察到HT-2毒素的血浆水平高于定量限。T-2毒素和T-2三醇的t(1/2λz)分别为23.40±2.94分钟和87.60±29.40分钟。在13.20±4.80分钟和38.40±15.00分钟的Tmax时,观察到T-2毒素和T-2三醇的血浆峰浓度(Cmax)分别为53.10±10.42纳克/毫升和47.64±9.19纳克/毫升。T-2毒素的绝对口服生物利用度较低(17.07%)。结果表明,T-2毒素在肉鸡体内吸收迅速,且大部分T-2毒素被广泛转化为代谢产物。

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