泰拉霉素在鸡体内的药物代谢动力学研究

Pharmacokinetic and bioavailability study of tulathromycin in chickens

[目的]探讨泰拉霉素在鸡体内的药物代谢动力学过程和特征及其生物利用度。[方法]给受试健康鸡分别进行静脉注射、肌肉注射及口服泰拉霉素,给药后在120 h内分点心脏采血,血浆样品经乙腈-0.1%甲酸溶液(体积比为95∶5)沉淀,离心去蛋白,以HPLC-ESI-MS/MS法检测鸡血浆中泰拉霉素含量,最后采用药动学软件Winnonlin的非房室模型进行数据分析。[结果]受试鸡经静脉注射、肌肉注射和口服给药后药时数据均适合非房室模型。静脉注射给药后,血浆清除率(CL)为17.71 m L·kg-1·h-1,稳态表观分布容积(Vss)为77.15 L·kg-1,消除半衰期(t1/2)为21.65 h。肌肉注射和口服泰拉霉素后,在0.25和0.5 h时,血浆浓度(Cmax)达峰值,分别为0.83和0.69 ng·m L-1,血浆中t1/2平均分别为20.96和24.33 h;生物利用度分别为92.59%和62.38%,说明肌肉注射给药较口服吸收完全,生物利用度高。[结论]泰拉霉素肌肉注射或口服在健康鸡体内表观分布容积大,吸收和分布迅速,达峰时间短,消除缓慢,生物利用度高。

[ Objectives ] Pharmacokinetics characteristics and bioavailability of the triamilide antimicrobial, tulathromycin were inves- tigated in healthy chickens. [ Methods ] A total of 306 healthy chickens were allotted to 3 groups at 102 chickens per group and received tulathromycin following single intravenous,intramuscular and oral administration at the dose of 20 mg·kg^-1 of body weight respectively. Blood samples were collected at different time points in 120 h after administration, then treated with acetonitrile and centrifuged to removal proteins and tulathromycin concentrations were determined by high-performance liquid chromatography （HPLC） with tandem mass pectrometry detection （LC-MS/MS）using ESI with a limit of detection of 1.67 ng·mL^-1 and a limit of quantitation of 2.96 ng· mL^-1. Pharmacokinetic parameters were estimated using the Winnonlin software package. [ Results] The tulathromycin concentration-time data were all fitted to noncompartment model after single intravenous,intramuscular and oral admin- istration to the healthy chickens. There is summary of the mean plasma pharmacokinetic parameters in chickens with a single intra- muscular, intravenous and oral administration of tulathromycin at 20 mg·kg^-1. The mean pharmacokinetic parameters of tulathromycin after intravenous administration in chicken were as fallows：area under the curve （AUCI=t ）was 5.34μg· h· mL^-1 ; cloral （CL）was 17.71 mL·kg^-1· h^-1 ;the volume of distribution at steady-state（ Vss ）was 77.15 L·kg^-1 and the elimination t1/2 was 21.65 h. The mean pharmacokinetic parameters of tulathromycin after intramuscular administration in chickens were as follows：t1/2 20.96 h ;AUClast 4.93μg· h· mL^-1 ： tmax was 0.25 h; Cmax was 0. 83μg·mL^-1. The mean pharmacokinetic parameters of tulathromycin after oral administration in chickens were as follows：t1/2 was 24.33 h;AUClast was 3.43μg·h·mL^-1 ;tmax was 0.50 h;Cmax was 0.69μg· mL^-1. The bioavailability of tulathromycin after single intramuscular and oral administration were 92.59% and 62.38% ,respectively. Tulath- romycin has shown higher efficacy by intramuscular than oral administration. The results of studies showed that pharmaeokinetics characteristics of tulathromycin in healthy chickens were rapidly absorption and wide distribution and slow elimination after single intravenous,intramuscular and oral administration in healthy chickens. The drug exhibited large volume of distribution and was absorbed completely from the injection site and had high bioavailability after single intramuscular administration compared with oral administration in chickens. The bioavailability of tulathromycin by intramuscular was higher than oral administration obviously. [ Conelusions]Tulathromycin is a novel triamilide antimicrobial that has been approved for use in the treatment and prevention of bovine and swine respiratory diseases. No one discovers any reports concerning tulathromycin about chickens at the present time. The study explores the pharmacokinetics characteristics and bioavailability of tulathromycin in chickens following single intravenous, intramuscular and oral administration for the first time ,which will provide reasonable reference for veterinary clinical study.