盐酸多西环素缓释注射液在猪体内的药物动力学

Pharmacokinetics of doxycycline hydrochloride sustain-released injection in swine

健康猪6头,体质量(17.8±1.3)kg,按拉丁方设计进行单剂量静注、肌注盐酸多西环素注射液(普通制剂)和肌注盐酸多西环素缓释注射液,注射剂量按多西环素计均为20 mg/kg,比较盐酸多西环素缓释注射液和盐酸多西环素注射液在猪体内的药动学特征和生物利用度。用高效液相色谱法测定其血药浓度,试验所得的血药浓度-时间数据采用非房室模型统计矩原理分析处理。猪静注盐酸多西环素注射液的主要药物动力学参数为:AUC(108.15±13.25)mg.h.L-1,MRT(5.56±1.08)h,Cl(0.19±0.02)L.h-1.kg-1,Vd(ss)(1.04±0.09)L.kg-1,t1/2(4.07±0.65)h。猪肌注盐酸多西环素注射液和盐酸多西环素缓释注射液的主要药物动力学参数分别为:MRT(15.18±2.13)h和(22.25±3.49)h;Tmax(1.13±0.44)h和(2.0±0.63)h;Cmax(3.32±0.33)mg.L-1和(3.10±0.29)mg.L-1;AUC(38.91±4.35)mg.h.L-1和(61.72±10.16)mg.h.L-1;F(36.66±7.88)%和(57.66±10.75)%。比较盐酸多西环素注射液和盐酸多西环素缓释注射液的主要药动学参数,除了Cmax以外,MRT、Tmax、AUC、F等主要参数均有显著的统计学意义(P<0.05)。这表明盐酸多西环素缓释注射液肌注后吸收缓慢,消除半衰期延长,临床用药48 h给药1次仍能维持对常见病原菌的有效血药浓度。

The pharmacokinetics of doxycycline was investigated in 6 healthy pigs in a latine square desigh following the single intravenous,intramuscular administration of doxycycline hydrochloride injection and single intramuscular administration of doxycycline hydrochloride sustain-released injection,each administration is at a dose of 20 mg/kg body weight.The plasma concentrations of doxycycline were determined by HPLC with UV detection at 365 nm.The plasma concentration-time data derived from experiments were analyzed by non-compartmental method based on statistical moment theory.The main pharmacokinetic parameters after intravenous administration were as follows：AUC（108.15±13.25） mg·h·L^-1,MRT（5.56±1.08） h,Cl（0.19±0.02） L·h^-1·kg^-1,Vd（ss）（1.04±0.09） L·kg^-1,t1/2（4.07±0.65） h.The main pharmacokinetic parameters of the doxycycline hydrochloride injection and the doxycycline hydrochloride sustain-released injection administration were as follows,respectively：MRT（15.18±2.13） h and（22.25±3.49） h;Tmax （1.13±0.44） h and（2.0±0.63） h;Cmax（3.32±0.33） mg·L^-1 and（3.10±0.29） mg·L^-1;AUC（38.91±4.35） mg·h·L^-1 and（61.72±10.16） mg·h·L^-1;F（36.66±7.88）% and（57.66±10.75）%.Comparing the main pharmacokinetic parameters of the doxycycline hydrochloride injection and the doxycycline hydrochloride sustain-released injection,the results showed there were significant differences in MRT,Tmax,AUC,F.These differences indicated that the doxycycline hydrochloride sustain-released injection is absorbed slowly and could be injected once every other day in the treatment of infectious diseases of swine.