巯甲丙脯酸生物黏附型缓释胶囊大鼠体内药动学研究

目的:建立高效液相色谱-紫外检测器法检测大鼠灌胃巯甲丙脯酸生物黏附型缓释胶囊(CBSRCs)后巯甲丙脯酸(Cap)的血药浓度的方法,并进行药动学研究。方法:30只大鼠随机分组,分别单剂量灌胃CBSRCs和巯甲丙脯酸普通片(COT)各5mg·kg-1,高效液相色谱法测定各时间点血药浓度,DAS2.0药动学软件计算出相应的药动学参数,并用t检验比较数据。结果:Cap检测浓度线性范围为12.5～800μg·L-1(r=0.9987),最低检测限12.5μg·L-1,平均回收率为99.40%,RSD<8.60%。灌服CBSRCs和COT后tmax分别为(3.12±0.67)、(1.53±0.27)h,Cmax(722.97±133.68)、(1114.47±208.36)μg·L-1,t1/2α(1.88±0.38)、(1.15±0.21)h,t1/2β(3.76±0.75)、(2.87±0.59)h,CL(2.87±0.51)、(3.43±0.67)L·h-1,Vd(10.98±1.90)、(13.21±2.57)L,AUC0～t(4856.03±835.46)、(4616.29±915.49)μg·h·L-1,MRT(5.53±1.03)、(3.71±0.66)h,各参数两两比较均有显著性差异(P<0.05或<0.01)。结论:高效液相色谱-紫外检测器法测定Cap浓度的方法稳定,结果准确可靠;与普通制剂比较,CBSRCs具有缓释和长效性。

Pharmacokinetic Study of Captopril Bioadhesive Sustained-release Capsules in Rats

OBJECTIVE： To establish an HPLC-UVD method for the determination of plasma concentration of captopril （Cap） in rats administrated with Captopril bioadhesive sustained-release capsules （CBSRCs） via i.g and study its pharmacokinetics. METHODS： 30 rats were randomly given oral signal dose of 5 mg·kg^-1 CBSRCs or 5 mg·kg^-1 Captopril oral tablets （COT）. The plasma concentration of Cap was measured by HPLC. The pharmacokinetics parameters of two preparations were calculated using DAS 2.0 software and compared in t-test. RESULTS： The linear range of Cap was 12.5-800 μg.L^-1（r=0.998 7） with an average recovery of 99.40% （RSD〈8.60%）. Minimum detectable concentration was 12.5 μg·L^-1. Main pharmacokinetics parameters of CBSRCs vs. COT were as follows： tmax： （3.12 ± 0.67） VS. （1.53 ± 0.27 ） h; Cmax（722.97± 133.68） vs. （1 114.47 ± 208.36） μg·L^-1; t1-2 （1.88± 0.38） vs. （1.15 ±0.21 ） h; ＆2,（3.76± 0.75） vs. （2.87± 0.59） h; CL（2.87± 0.51） vs. （3.43± 0.67 ）L. h^-1; Vd（10.98 ± 1.90） vs. （13.21 ± 2.57） L; AUC0-1（4 856.03±835.46） vs. （4 616.29 ± 915.49） μg.h.L^-1; MRT（5.53±1.03） vs. （3.71 ± 0.66） h. Significant difference was noted in pharmacokinetic parameters （P〈0.05 or P〈0.01 ）. CONCLUSION： The HPLC-UVD method is accurate and reliable for the determination of plasma concentration of Cap. As compared with COT, CBSRCs shows sustained-release and long-term effect characteristic.