卡托普利生物黏附型缓释胶囊大鼠体内药动学研究

Pharmacokinetic Study of Captopril/Bioadhesive Sustained-Release Capsules in Rats

研究卡托普利生物黏附型缓释胶囊(Captopril/bioadhesive sustained-release capsules,CBSRCs)在大鼠体内的药动学,通过建立高效液相色谱(HPLC)-紫外检测法测定卡托普利(Captopril,Cap)的血药浓度,研究了大鼠灌胃CBSRCs和卡托普利普通片(Captopril ordinary tablet,COT)各5 mg/kg后16 h内的药动学,DAS 2.0软件计算出相应的药动学参数,t检验比较两种制剂的药动学参数。结果表明,Cap浓度在12.5～800μg/L范围内线性关系良好(r=0.998 7),最低检测限为12.5μg/L,平均回收率为99.40%,平均日内RSD为3.97%,平均日间RSD为4.84%;单剂量口服CBSRCs和COT,Tmax分别为(3.12±0.67),(1.53±0.27)h;Cmax为(722.97±133.68),(1 114.47±208.36)μg/L;T1/2α为(1.88±0.38),(1.15±0.21)h;T1/2β为(3.76±0.75),(2.87±0.59)h;CL为(2.87±0.51),(3.43±0.67)L/h,Vd为(10.98±1.90),(13.21±2.57)L;AUC0-t为(4 856.03±835.46),(4 616.29±915.49)μg.h/L;AUC0-∞为(5 218.39±1 037.58),(4 705.83±894.56)μg.h/L。CBSRCs和COT相比,T1/2α,T1/2β,AUC0-t,AUC0-∞,CL,Vd,Tmax,Cmax差异显著(P<0.05或0.01)。说明CBSRCs与市售COT在大鼠体内的药动学特征差异具有显著性,说明高效液相色谱-紫外检测器测定Cap含量的方法稳定,结果准确可靠。CBSRCs与市售COT相比,CBSRCs显著改善了卡托普利原药的药动学性质,具有缓释和长效的作用。

For the purpose of investigating the pharmacokinetics of captopril/bioadhesive sustained-re-lease capsules（CBSRCs）,An HPLC process with UV detection was established for the determination of plasma concentration of captopril in rats.After CBSRCs and Captopril ordinary tablet（COT） were orally administrated to rats at a single dosage of 5 mg/kg respectively,their pharmacokinetic behaviors in 16 h were examined.The pharmacokinetics parameters were calculated and analyzed by DAS 2.0 software.Linear calibration curves of Cap were described as follows：Y=0.006 5x-0.038 2,r=0.998 7.Minimum detectable concentration was 12.5μg/L.Mean recovery was 99.40% for both Cap and internal standard.The variation of recovery between different concentrations of Cap and internal standard was both5%（n =7）.Mean relative standard deviation（interday） was 3.97%（n=7）.Mean relative standard deviation（day to day） was 4.84%（n= 7）.The major pharmacokinetics parameters of CBSRCs and COT were shown as follows： Tmaxwere（3.12±0.67） and（1.53±0.27） h,respectively;Cmaxwere（722.97±133.68） and（111 4.47±208.36）μg/L,respectively;T1/2αwere（1.88±0.38） and（1.15±0.21） h,respectively;T1/2βwere（3.76±0.75） and（2.87±0.59） h,respectively;CL were（2.87±0.51） and（3.43±0.67） L/h,respectively,Vdwere（10.98±1.90） and（13.21±2.57） L,respectively;AUC0-twere（4 856.03±835.46） and（4 616.29±915.49）μg.h/L,respectively;and AUC0-∞were（5 218.39±1 037.58） and（4 705.83 ±894.56）μg.h/L respectively.The T1/2α,T1/2β,AUC0-t,AUC0-∞,CL,Vd,Tmaxand Cmaxof CBSRCs were all significantly different repectively from those of COT（P0.05 or 0.01）.The results showed that the process of determination with HPLC was stable and reliable results can be obtained.CBSRCs showed the characteristics of sustained-release and higher efficiency compared with COT.