Wang Liye, Wen Lihua, Pan Yuanhu, Wang Zhenzhen, Zhou Kaixiang, Mi Kun, Liu Zhenli, Qu Wei, Huang Lingli
National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, China.
College of Food and Drug, Luoyang Normal University, Luoyang, China.
Front Vet Sci. 2022 Jan 18;8:799773. doi: 10.3389/fvets.2021.799773. eCollection 2021.
Diaveridine (DVD) is widely used for the prevention and treatment of coccidiosis and leucocytozoonosis infections in food-producing animals. To gain a better understanding of DVD metabolism and pharmacokinetics in healthy Landrace/Doric Cross castrated male pigs and both female and male Cobb 500 broiler chickens, a method involving radioactive tracing coupled with LC/MS-IT-TOF was developed for the identification and quantitation of DVD and its metabolites in pig and chicken plasma, and then was applied to investigate DVD pharmacokinetics. A simple MCX solid phase extraction procedure was adopted for sample preparation. After a single oral administration of H-DVD (10 mg/kg BW), three radioactive compounds (D0: DVD; D1: 3'-desmethyl-DVD; and D2: monoglucuronide of 3'-desmethyl-DVD) were identified in pig plasma, while only two radioactive compounds (D0 and D2) were identified in chicken plasma. In both species, the values for all detected compounds were reached at 2 h after dosing. The order was D2 (1.38 μg/ml) > D0 (0.49 μg/ml) > D1 (0.24 μg/ml) in pigs and D0 (1.55 μg/ml) > D2 (0.27 μg/ml) in chickens. The longer (elimination half-life) of D0 contributed to the slow elimination of DVD-related compounds. The of D0 in pigs (66.41 h) was significantly longer than that in chickens (48.30 h), but the of total DVD-related metabolites in pigs (42.86 h) was lower than that in chickens (56.11 h). These findings suggested that the metabolism and pharmacokinetics of DVD in pigs and chickens were significantly different, and that this would affect its effectiveness, toxicology, and food safety in these animals.
二硝托胺（DVD）广泛用于预防和治疗食用动物的球虫病和住白细胞原虫病感染。为了更好地了解DVD在健康长白/多里克杂交去势雄性猪以及雌性和雄性科宝500肉鸡中的代谢和药代动力学，开发了一种放射性示踪结合LC/MS-IT-TOF的方法，用于鉴定和定量猪和鸡血浆中的DVD及其代谢物，然后将其应用于研究DVD的药代动力学。采用简单的MCX固相萃取程序进行样品制备。单次口服H-DVD（10mg/kg体重）后，在猪血浆中鉴定出三种放射性化合物（D0：DVD；D1：3'-去甲基-DVD；D2：3'-去甲基-DVD的单葡萄糖醛酸苷），而在鸡血浆中仅鉴定出两种放射性化合物（D0和D2）。在两个物种中，所有检测到的化合物的Cmax值在给药后2小时达到。猪中的顺序为D2（1.38μg/ml）>D0（0.49μg/ml）>D1（0.24μg/ml），鸡中的顺序为D0（1.55μg/ml）>D2（0.27μg/ml）。D0的较长t1/2（消除半衰期）导致与DVD相关的化合物消除缓慢。猪中D0的t1/2（66.41小时）显著长于鸡中（48.30小时），但猪中总DVD相关代谢物的AUC（42.86小时）低于鸡中（56.11小时）。这些发现表明，DVD在猪和鸡中的代谢和药代动力学存在显著差异，这将影响其在这些动物中的有效性、毒理学和食品安全。
