复方磺胺间甲氧嘧啶(CO.SMM)缓释型注射液在水牛体内的血浆药动学

Pharmacokinetics of CO.SMM sustained-release injection in buffaloes plasma

为研究复方磺胺间甲氧嘧啶(CO.SMM)缓释型注射液的药代动力学规律,选择健康水牛8头,随机分成2组(n=4),对照组和试验组分别按50mg/kg剂量肌注单方SMM和CO.SMM缓释型注射液,采用高效液相色谱法测定血浆药物浓度。利用药代动力学程序软件3P97处理药时数据,计算药代动力学参数。结果显示:(1)肌注单方SMM注射液后药时数据符合一级吸收二室开放模型,t1/2Ka0.47h,t1/2β3.25h,AUC261.19h·μg·mL-1,Vd0.89L/kg,CLB0.19L·kg-1·h-1,tmax1.02h,Cmax76.85mg/L。(2)肌注CO.SMM缓释型注射液后,SMM药时数据符合一级吸收一室开放模型,t1/2Ka0.41h,t1/2β11.46h,AUC1107h·μg·mL-1,Vd0.75L·kg-1,CLB0.05L·kg-1·h-1,tmax2.03h,Cmax59.24μg.mL-1;肌注CO.SMM缓释型注射液后,TMP药时数据符合一级吸收二室开放模型,t1/2Ka0.87h,t1/2β19.59h,AUC83.66h·μg·mL-1,Vd16.89L·kg-1,CLB0.60L·kg-1.h-1,tmax2.95h,Cmax4.15μg·mL-1。结果表明,CO.SMM缓释型注射液肌注水牛后SMM在体内消除缓慢,达峰时间延迟,血药浓度平稳,具有缓释、增效的作用。

Blood samples were collected at different intervals after administration, and the concentrations of SMM and TMP in plasma were determined by high performance liquid chromatography （HPLC） and the pharmacokinetic program 3P97 was used to analyse the concentrations versus time data. The results revealed that the concentration-time data of SMM and TMP were respectively described by a one-compartment open model with firstorder absorption and two-compartment open model with first-order absorption after single intramuscular administration of CO. SMM sustained-release injection, and the main pharmacokinetic parameters of SMM and TMP in CO. SMM sustained-release injection were as follows： t1/2Ka 0.41 h,t1/2β 11.46 h,AUC 1 107 h ·μg· mL^-1 ,Vd 0.75 L · kg^-1,CLB0.05L· kg^- 1 · h^-1,tmax 2.03h,Cmax 59.24 μg· mL ^-1,and t1/2Ka. 0. 47 h,t1/2β 3. 25 h,AUC 261.18h· μg· mL^- 1,Vd 0.89 L · kg ^-1,CL, 0.19 L · kg^- 1 · h^-1,tmax 1.02 h,Cmax 76.85 μg· mL^-1, and the concentrationtime data of SMM was described by two-compartment open model with first-order absorption after single intramuscular administration of SMM and the main pharmacokinetic parameters were as follows： t1/2K 0. 47 h,t1/2β 3.25 h, AUC 261.18 h · μg · mL^- 1,Vd 0.89 L · kg^-1,CLB 0.19 L · kg^- 1· h^-1,tmax 1.02 h,Cmax 76.85 μg· mL 7, which indicated that the absorption half-life of SMM in the two preparations had no significant difference （P 〉 0.05）, but the elimination half-life and peak time of SMM in CO. SMM sustained-release injection were significantly longer than SMM injection （P 〈 0.01 ）, and the Cmax of the latter was significantly higher than the former （P〈 0.01 ）, so in vivo SMM released slowly, delayed the time of peaking, elimited slowly and sustained the blood drug level after intramuscular administration of CO. SMM. All these demonstrated that CO. SMM sustained-release injection has the sustained-release-long-acting property.