替米考星颗粒在猪体内的药代动力学研究

Pharmacokinetics of tilmicosin granula in swines

关键词:  替米考星  高效液相  猪  药代动力学  生物等效性

Key words:  tilmicosin  HPLC  swine  pharmacokinetics  bioequivalence

摘要:

研究20%树脂包被替米考星颗粒在猪体内的药代动力学特性并评价其(受试制剂T)与国际(R1)国内(R2)两种参比制剂的生物等效性。采用随机三制剂、三周期自身交叉试验设计,选取6头健康的阉割过的小公猪(体重20.7±2.6kg)分别口灌给药三种制剂(10 mg.Kg_^-1bw),采用HPLC测定血浆替米考星浓度,利用Kinetica 5.0分析药代动力学特性及生物等效性评价。20%树脂包被替米考星颗粒在猪体内的药时曲线符合带一级吸收的二室开放模型；T、R1、R2的C_max分别为(0.2830±0.0292)、(0.2815±0.0291)、(0.4087±0.0421)μg.mL_^-1 ,t_max分别为(4±0.9832)、(0.75±0.1581)、(1±0.2458)h,AUC_0-∞分别为(10.8715±1.1203)、(9.8715±1.0173)、(10.6441±1.096 9)μg.h.mL_^-1；受试制剂相比于两种参比制剂的相对生物利用度分别为110.13±6.04%(R1)和102.63±9.64%(R2)。 结果表明三种制剂间具备生物等效性；20%树脂包被替米考星颗粒有更好的缓释作用,具有一定的生物安全性,在体内保持药效时间更久。

Abstract:

The pharmacokinetics of tilmicosin granula coated with 20% resin (test formulation, T) in swines were investigated and the bioequivalence of T and the other two similar products at home (reference formulation 2, R2) and abroad (reference formulation 1, R1) were also evaluated. A randomized three-period and three-way crossover self-controlled design was employed. Six healthy castrated male pigs (average body weight 20.7±2.6 kg) were selected to take three formulations by oral administration separately(10 mg.Kg^-1bw). The plasma concentrations of tilmicosin were analyzed by HPLC. The pharmacokinetic parameters and bioequivalence were calculated with Kinetica5.0. The concentration-time curve of tilmicosin granula coated with 20% resin fitted a two-compartment open model with first-order absorption. The main pharmacokinetic parameters of T, R1, R2 were as follows, Cmax as (0.2830±0.0292), (0.2815±0.0291), (0.4087±0.042 1) μg.mL^-1, tmax as(4±0.9832), (0.75±0.1581), (1±0.2458)h, AUC0-∞ as (10.8715±1.1203), (9.8715±1.0173), (10.6441±1.0969)μg.h.mL^-1. The relative bioavailability of R1 and R2 were 110.13±6.04% and 102.63±9.64%. In Conclusion, the three formulations are bioequivalent. Tilmicosin granula coated with 20% resin shows better performance of sustained-release, which improves biosafety and last longer.