甘草酸磷脂复合物自乳化胶囊与肠溶胶囊的药动学比较

Comparison of the Pharmacokinetics Between Glycyrrhizic Acid Phospholipid Complex Self Emulsifying Capsule and Enteric Coated Capsule

关键词:  甘草酸磷脂复合物  自乳化制剂  高效液相色谱  药动学

Key words:  glycyrrhizic acid phospholipid complex  self emulsifying preparation  HPLC  pharmacokinetics

摘要:

目的 以市售甘草酸二铵肠溶胶囊为参比制剂，考察自制甘草酸磷脂复合物自乳化胶囊在Beagle犬体内的相对生物利用度。方法 Beagle犬6只，自身交叉对照、单剂量灌胃甘草酸磷脂复合物自乳化胶囊或市售肠溶胶囊。采用HPLC测定血浆中的甘草酸浓度，DAS 2.0程序拟合药代动力学数据。结果 参比制剂和受试制剂主要的药动学参数：T_max分别为(6.00±0.000)h，(2.917±0.585)h；C_max分别为(12.756±1.075)mg·L^-1，(17.751±1.604)mg·L^-1；AUC_0-t分别为(150.894±22.850)mg·h·L^-1，(211.196±40.880)mg·h·L^-1；AUC_0-∞分别为(159.39±21.862)mg·h·L^-1，(221.287±42.164)mg·h·L^-1，甘草酸磷脂复合物自乳化制剂相对生物利用度(F%)为139.76%。结论 Beagle犬体内甘草酸的药动学规律均符合一级吸收二室模型，与市售胶囊剂相比，自乳化制剂的C_max、AUC_0-t，AUC_0-∞均高于肠溶胶囊，表明自乳化制剂能显著提高药物的生物利用度，初步达到了设计要求。

Abstract:

OBJECTIVE To compare the pharmacokinetics between glycyrrhizic acid phospholipid complex self emulsifying preparation(T) and glycyrrhizic acid diammonium enteric coated capsule(R) in dogs. METHODS Six Beagle dogs were given orally T and R, with a single dose of 50 mg·kg^-1 glycyrrhizic acid in self crossover study. The plasma concentration of glycyrrhizic acid was assayed by HPLC and the pharmacokinetic parameters were calculated with DAS2.0 program. RESULTS T_max for R and T were (6.00±0.000)h and (2.917±0.585)h; C_max for R and T were (12.756±1.075)mg·L^-1 and (17.751±1.604)mg·L^-1, respectively; AUC_0-t were (150.894±22.850)mg·h·L^-1 and (211.196±40.880)mg·h·L^-1; AUC_0-∞ were (159.39±21.862)mg·h·L^-1 and (221.287±42.164)mg·h·L^-1; the relative bioavailability of T was 139.76%. CONCLUSIONS The pharmacokinetics of glycyrrhizic acid in dogs accorded with the two compartment models and with the first-order absorption after T or R administration orally, C_max, AUC_0-t and AUC_0-∞ of T were all higher than those of R, and T had a higher bioavailability, which reached the object of this task.