替米考星静脉及皮下注射后在绵羊体内的药代动力学研究

The Pharmacokinetics of Tilmicosin Administrated Intravenously and Subcutaneously in Healthy Sheep

健康成年杂交绵羊静脉和皮下注射替米考星注射液后,用反相高效液相色谱法测定不同时间点血清中的药物浓度。采用3p97药代动力学程序软件处理数据,替米考星两种给药途径的药 时数据均符合二室开放模型静脉注射给药(5 mg/kg bw)的主要药代动力学参数: t1/2a 为 0. 611±0. 017 h、t1/2β为 23. 215±0. 459 h、AUC为11 815±0.396(μg/mL)·h、CL(s)为 0.424±0.014 L/(kg·h)。替米考星皮下注射主要药代动力学参数: 1mg/kg bw剂量组 t1/2a 为 1 751±0 557 h、t1/2β为 22 896±2 747 h、t1/2Ka 为 0. 100±0. 025 h、AUC 为 25. 828±1 479 (μg/mL)·h、CL(s)为0.393±0.017 L/(kg·h),Tmax为0.500±0.065 h,Cmax为1.424±0.156μg/mL、F为109.28%±6.25%。30 mg/kg bw剂量组 t1/2a为1.342±0.244 h、t1/2β为 20.052±1.236 h、t1/2Ka为 0.086±0.015h、AUC为57 575±6.760 (μg/mL)·h、CL(s)为0.527±0.068 L/(kg·h)、Tmax为0.437±0.039 h、Cmax为 3.343±0 512μg/mL、F为81.22%±9.54%。结果表明,绵羊静脉和皮下注射替米考星体内分布广,消除缓慢;皮下注射后在体内吸收迅速,达峰快,生物利用度高。

Tilmicosin was administrated intravenously (i.v.) and subcutaneously (s.c.) to adult healthy crossed sheep to determine its serum concentrations by a high performance liquid chromatography (HPLC) method. Pharmacokinetic analysis of serum concentration-time data after i.v. and s.c. administration was carried out using a computer program (3p97,China Pharmacology Association). Serum concentration-time data after i.v. and s.c.administration were best described by a two-compartment open model.After i.v. injection of 5 mg/kg bw,the parameters were as follows, t_(1/2a)0.611±0.017 h,t_(1/2β) (23.215)±0.459 h,AUC 11.815±0.396(μg/mL)·h, CL(s) 0.424±0.014 L/(kg·h).After s.c. injections of 10 mg/kg bw, the parameters were: t_(1/2a)1.751±0.557 h,t_(1/2β)22.896±2.747 h,t_(1/2Ka) 0.100±0.025 h,AUC 25.828±1.479(μg/mL)·h,CL(s)0.393±0.017 L/(kg·h),T_(max)0.500±0.065 h,C_(max)1.424±0.156 (μg/mL), F was 109.28%±6.25%. After s.c. injections of 30 mg/kg bw, the parameters were: t_(1/2a)1.342±0.244 h,t_(1/2β)20.052±1.236 h,t_(1/2Ka) 0.086±0.015 h,AUC 57.575±6.760(μg/mL)·h, CL(s)0.527±0.068 L/(kg·h),T_(max)0.437±0.039 h, C_(max)3.343±0.512 μg/mL, F was 81.22%±9.54%.The results showed that tilmicosin was Absorbed quickly, distributed widely and eliminated slowly in sheep after i.v. and s.c. administrations; The bioavailability of tilmicosin after s.c. administrations of 10 and 30 (mg/kg) (b w) were 109.28%±6.25% and 81.22%±9.54%, respectively, indicating that tilmicosin was almost Absorbed completely.