泰拉霉素在猪体内的药动学特征及其血浆蛋白结合率的研究

Studies on pharmacokinetics and plasma protein binding rate of tulathromycin in swine

本研究旨在比较自制泰拉霉素注射液和瑞可新注射液在猪体内的药代动力学特征,并测定泰拉霉素在猪体内的血浆蛋白结合率。18头健康猪被随机分为3组,分别进行单剂量(2.5 mg/kg)静脉注射、肌内注射泰拉霉素注射液和肌内注射瑞可新注射液,超高效液相色谱-串联质谱(UPLC-MS/MS)法测定猪血浆中泰拉霉素的浓度,采用药动学软件Winnonlin 5.2.1处理血浆药物浓度-时间数据,并计算出有关药动学参数。采用超滤法考察泰拉霉素在猪体内的血浆蛋白结合率。结果,静脉注射自制泰拉霉素注射液后,其主要药动学参数为t_(1/2β)=72.20 h±20.35 h,AUC_(last)=11.31 g·h/mL±4.20 g·h/mL,MRT=72.01 h±14.81 h。肌内注射泰拉霉素注射液和瑞可新注射液后的主要药动学参数如下,t_(max)分别为0.50 h±0.22 h,0.22 h±0.07h;C_(max)分别为1.18 g/mL±0.55 g/mL,1.81 g/mL±0.68 g/mL;AUC_(last)分别为10.85 g·h/mL±4.76g·h/mL,12.06 g·h/mL±3.08 g·h/mL;t1/2β分别为68.59 h±14.29 h,68.01 h±15.10 h。与瑞可新相比,自制泰拉霉素注射液相对生物利用度为92.95%±16.89%,绝对生物利用度为93.90%±19.11%。上述结果表明,猪肌内注射泰拉霉素后吸收迅速,体内分布广泛,消除缓慢,生物利用度高;自制泰拉霉素注射液与瑞可新的药动学特征相似,生物利用度相当;泰拉霉素的血浆蛋白结合率高达95.17%,属于高蛋白结合率化合物且无浓度依赖性。

The study aims to investigate pharmacokinetics of tulathromycin injection and draxxin injection,and to determine the plasma protein binding rates in swine.Eighteen pigs were randomly divided into three groups and received 2.5 mg/kg of tulathromycin injection by either intravenous （i.v.） or intramuscular （i.m.） route,and six pigs were injected the same dosage of draxxin injection following i.m.administration.The plasma concentrations of tulathromycin was determined by ultra-high pressure liquid chromatography tandem mass spectrometry method （UPLC-MS/MS）.The pharmacokinetic parameters were calculated by Winnonlin 5.2.1 software.Ultrafiltration was applied to determine the plasma protein binding rate of tulathromycin in swine.In result,following intravenous administration,the mainpharmacokinetic parameters were as follows：t（1/2）β=72.20 h±20.35 h,AUC（last）=11.31 g·h/mL±4.20 g·h/mL,and MRT=72.01 h±14.81 h.The main pharmacokinetic parameters for tulathromycin injection and draxxin injection administrated intramuscularly were as follows∶t（max）=0.50 h±0.22 h and 0.22 h±0.07h;C（max）=1.18 g/mL±0.55 g/mL and 1.81 g/mL±0.68 g/mL,AUC（last）=10.85 g·h/mL±4.76 g·h/mL and 12.06 g·h/mL±3.08 g·h/mL,and t（1/2β）=68.59 h±14.29 h and 68.01 h±15.10 h.Compared with draxxin injection,the relative bioavailability was 92.95%±16.89%,and the absolute bioavailability was 93.90%±19.11%.In conclusion,tulathromycin was absorbed quickly,distributed widely,eliminated slowly and highly bioavailable after i.m.administration.The pharmacokinetics and bioavailability of two injections of tulathromycin are similar.The plasma protein binding rate of tulathromycin was above95.17%,and it had the high binding ability and nonconcentration-dependent characteristic.