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亚硒酸钠经口给药在缺硒雏鸭血液和组织中的药代动力学。

Pharmacokinetics of Sodium Selenite Administered Orally in Blood and Tissues of Selenium-Deficient Ducklings.

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.

College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People's Republic of China.

出版信息

Biol Trace Elem Res. 2019 Aug;190(2):509-516. doi: 10.1007/s12011-018-1567-8. Epub 2018 Nov 22.

DOI:10.1007/s12011-018-1567-8
PMID:30465172
Abstract

Selenium (Se) is an essential trace element for humans and animals. Appropriate amount of Se in the body can prevent a variety of diseases. However, Se deficiency leads to pathological changes such as skeletal muscle necrosis and pancreatic atrophy in livestock and poultry. Se preparations are widely used in the prevention and treatment of Se-deficient disease, but there is no unified standard of medication, and the safe dose range of Se is narrow. Therefore, it is of great significance to study the pharmacokinetics of low-Se ducklings and to formulate drug administration schemes. In the present study, eighty 1-day-old healthy ducklings were randomly selected, and fed with low-Se diet to 30 days of age (blood Se content ≦ 0.03 μg/mL). After the low Se duckling models were duplicated, blood samples and tissues of livers, pancreases, and thigh muscles were collected at different time points to detect Se content following oral administration of 0.1% sodium selenite (NaSeO) at 0.8 mg/kg BW, and the pharmacokinetics parameters were automatically calculated by MCPKP program. The results showed that pharmacokinetics characteristics of NaSeO in blood, livers, and pancreases of ducklings were consistent with the first-order absorption and two-compartment open models; in thigh muscles was consistent with the first-order absorption and one compartment with a lag time open model. The primary kinetic parameters of NaSeO in blood: the half-life of absorption was 5.9026 h, the time of reaching maximum concentration was 23.03 h, and the half-life of elimination was 131.13 h. The absorption of NaSeO in livers was the quickest, pancreases and thigh muscles were in order of becoming slower, and the elimination of NaSeO in thigh muscles was the quickest, livers and pancreases were in order of becoming slower. The administration parameters of multi-dose were calculated according to the kinetic of single-dose: loading dose (D*) was 1.7046 mg/kg BW, maintenance dose (D) was 0.8 mg/kg BW, and dosing interval (τ) was 120 h. The results of this study can supplement and improve the theoretical system of Se metabolic kinetics, and provide experimental basis for the prevention and treatment of Se deficiency disease by rational drug use.

摘要

硒(Se)是人体和动物必需的微量元素。适量的硒可以预防多种疾病。然而,硒缺乏会导致家畜和家禽的骨骼肌坏死和胰腺萎缩等病理变化。硒制剂广泛用于预防和治疗硒缺乏症,但没有统一的用药标准,硒的安全剂量范围较窄。因此,研究低硒雏鸭的药代动力学并制定给药方案具有重要意义。本研究随机选择 80 只 1 日龄健康雏鸭,用低硒饲料喂养至 30 日龄(血硒含量≦0.03μg/mL)。复制低硒雏鸭模型后,分别于不同时间点采集口服 0.8mg/kg BW 0.1%亚硒酸钠(NaSeO)后雏鸭的血样和肝脏、胰腺、股四头肌组织,采用 MCPKP 程序自动计算药代动力学参数。结果表明,NaSeO 在雏鸭血液、肝脏和胰腺中的药代动力学特征符合一级吸收和双室开放模型;在股四头肌中符合一级吸收和一室有滞后时间的开放模型。NaSeO 在血液中的主要动力学参数:吸收半衰期为 5.9026 h,达峰时间为 23.03 h,消除半衰期为 131.13 h。NaSeO 在肝脏中的吸收最快,胰腺和股四头肌依次变慢,NaSeO 在股四头肌中的消除最快,肝脏和胰腺依次变慢。根据单剂量动力学计算多剂量给药参数:负荷剂量(D*)为 1.7046mg/kg BW,维持剂量(D)为 0.8mg/kg BW,给药间隔(τ)为 120 h。本研究结果可以补充和完善硒代谢动力学的理论体系,为合理用药防治硒缺乏症提供实验依据。

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