盐酸罗沙替丁醋酸酯缓释片的药动学研究

The pharmacokinetics study of roxatidine acetate hydrochloride sustained-release tablets

目的建立测定比格犬血浆中罗沙替丁浓度的高效液相色谱法,利用建立的方法研究比格犬服用盐酸罗沙替丁醋酸酯缓释片及缓释胶囊后的药物动力学特征,进行生物等效性评价。方法利用液液萃取法提取血浆中罗沙替丁,采用高效液相色谱法,流动相为水-乙腈-三乙胺-醋酸,色谱柱为C_(18)柱,内标为咖啡因,测定比格犬分别服用盐酸罗沙替丁醋酸酯缓释片及缓释胶囊后血浆中的血药浓度。结果血浆中罗沙替丁的质量浓度在100~6 000μg·L^(-1)内呈良好的线性关系,日内与日间精密度均小于15%,回收率在72.8~76.7%内。比格犬分别口服盐酸罗沙替丁醋酸酯缓释片150 mg及市售盐酸罗沙替丁醋酸酯缓释胶囊150 mg后,其ρmax分别3 032μg·L^(-1)和3 234μg·L^(-1);AUC_(0→t)分别为1.462 8×10~4μg·L^(-1)·h和1.446 4×10~4μg·L^(-1)·h;AUC_(0→∞)分别为1.609 6×10~4μg·L^(-1)·h和1.576 3×10~4μg·L^(-1)·h,t_(1/2)分别为3.21 h和3.16 h。结论应用高效液相色谱法成功的对比格犬分别口服盐酸罗沙替丁醋酸酯缓释片及缓释胶囊后的生物等效性进行评价,自制的盐酸罗沙替丁醋酸酯缓释片与市售缓释胶囊生物等效。

Objective To establish the method of determining the plasma concentrations of roxatidine in beagle dogs using high-performance liquid chromatography(HPLC). To study the pharmacokinetics of roxatidine acetate hydrochloride sustained-release tablets and capsules in beagle dogs,and evaluate the bioequivalence. Methods Liquid-liquid extraction method was used to extract roxatidine. The plasma concentrations of roxatidine in beagle dogs were detected by HPLC. The mixed solution of water,acetonitrile,triethylamine and acetic acid was selected as mobile phase using C_(18) chromatographic column,and caffeine was chose as the internal standard. Results The serum concentration of roxatidine from 100 to 6 000 μg·L^(-1) showed good linear relationship. The precisions of intra-and inter-day were both less than 15%. The recovery was between 72.8 and 76.7%. Pharmacokinetic studies of roxatidine sustained-release tablets(the dose was 150 mg) and roxatidine sustained-release commercial capsules(the dose was 150 mg) were conducted after oral administration in beagle dogs. ρmax were 3 032 μg·L^(-1) and 3 234 μg·L^(-1),AUC_(0→t) were 1.462 8×10~4 μg·L^(-1)·h and 1.446 4×10~4 μg·L^(-1)·h,AUC_(0→∞) were 1.609 6×10~4 μg·L^(-1)·h and 1.576 3×10~4 μg·L^(-1)·h,t_(1/2) were 3.21 h and 3.16 h,respectively. Conclusions HPLC method has been applied successfully on the bioequivalence evaluation for oral roxatidine sustained-release tablets and capsules in beagle dogs. It is concluded that the self-made sustained-release tablets and commercial capsules are biological equivalent.