泰妙菌素混悬注射液在猪体内的药物动力学及生物利用度研究

The Pharmacokinetics and Bioavailability of Injectable Tiamulin Suspension in Pigs

【目的】研究并比较泰妙菌素混悬注射液和泰妙菌素注射液在猪体内的药物代谢动力学特征及生物利用度。【方法】7头健康猪,按随机拉丁方设计,进行单次给药剂量(10mg·kg-1b.w)静注、肌注泰妙菌素注射液和肌注泰妙菌素注射混悬液,高效液相色谱串联质谱法测定猪血浆中泰妙菌素的浓度,罗红霉素作为内标,3P97药动学计算软件处理血浆药物浓度-时间数据。【结果】猪静注给药的药时数据符合无吸收三室开放模型,主要药动学参数为:t1/2β为2.04±0.23h,t1/2α为0.39±0.06h,t1/2π为0.12±0.04h,Vd为8.73±1.83L·kg-1,AUC为3.78±0.52μg·mL-1.h-1,ClB为2.99±0.43L·kg-1.h-1)。猪肌注泰妙菌素注射液的药时数据符合一级吸收二室开放模型,主要的药物动力学参数分别为:t1/2Ka(0.06±0.01)h,t1/2β(3.67±0.41)h,Tmax(0.18±0.03)h,Cmax(1.32±0.25)μg·mL-1,AUC(2.62±0.21)μg·mL-1.h-1,生物利用度为73.51%。猪肌注泰妙菌素混悬液的药时数据则符合一级吸收一室开放模型,主要的药物动力学参数为:t1/2Ka(0.04±0.01)h,t1/2Ke(2.90±0.43)h,Tmax(0.27±0.03)h,Cmax(0.7±0.11)μg·mL-1,AUC(2.80±0.35)μg·mL-1.h-1,生物利用度为75.73%。t检验比较肌注泰妙菌素注射液和泰妙菌素注射混悬液的主要药动学参数,结果表明,两者除达峰浓度Cmax有显著差异外,AUC、t1/2Ka、Tmax、t1/2Ke和生物利用度均无显著性差异。【结论】泰妙菌素注射混悬液肌注后在猪体内具有吸收迅速,体内分布广,达峰迅速,消除较快的药动学特征。

【Objective and method】 The pharmacokinetics and bioavailability of tiamulin were investigated and compared in 7 healthy pigs in a Latin square design following single intravenous （10 mg·kg^-1 b.w）,intramuscular （10 mg·kg^-1 b.w） administration of tiamulin injection and single intramuscular （10 mg·kg^-1 b.w） administration of tiamulin suspension. The tiamulin concentrations in plasma samples were determined by LC/APCI-MS. Roxithromycin was selected as internal standard. Pharmacokinetic analysis of plasma drug concentration-time data for tiamulin was carried out with a computer program 3P97. 【Result】 The tiamulin concentration-time data were fitted to a three-compartment open model after single intravenous administration of the tiamulin injection. The main pharmacokinetic parameters were as follows：t1/2β 2.04±0.23 h,t1/2α0.39±0.06 h,t1/2π0.12±0.04 h,Vd8.73±1.83 L·kg^-1,AUC3.78±0.52 μg·mL^-1·h^-1,ClB2.99±0.43 L·kg^-1·h^-1.The tiamulin concentration-time data were described by a two-compartment open model with first-order absorption after single intramuscular administration of the tiamulin injection. The main pharmacokinetic prameters of the tiamulin injection were as follows：t1/2Ka 0.06±0.01h,t1/2β 3.67±0.41 h,Tmax 0.18±0.03 h,Cmax1.32±0.25 μg·mL^-1,AUC 2.62±0.21 μg·mL-1·h^-1,and the bioavailability was 73.51%,respectively. For single intramuscular administration of the injectable tiamulin suspension,the tiamulin concentration-time data were described by a one-compartment open model with first-order absorption and the main pharmacokinetic parameter were as follows：t1/2Ka 0.04±0.01 h,t1/2Ke 2.90±0.43 h,Tmax 0.27±0.03 h,Cmax 0.7±0.11 μg·mL^-1,AUC 2.80±0.35 μg·mL-1·h^-1,and the bioavailability was 75.73%,respectively. The statistics t-test results showed that there were no significant differences in pharmacokinetics of tiamulin in pigs between two dosage forms except Cmax. 【Conclusion】 The results of present studies showed that the injectable tiamulin suspension demonstrated rapid absorption,extensive distribution and rapid elimination.