关键词: 泰妙菌素, 混悬注射液, 药物代谢动力学, 生物利用度, 猪

Abstract:

【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, Cmax 1.32±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.

Key words: tiamulin, injectable suspension, pharmacokinetics, bioavailability, pig