枸橼酸莫沙必利胃漂浮缓释微丸在大鼠体内的口服生物利用度研究

目的：建立大鼠血浆中莫沙必利药物浓度的HPLC-MS/MS测定方法，研究枸橼酸莫沙必利胃漂浮缓释微丸在大鼠体内的口服相对生物利用度。方法：12只大鼠按照随机数字表法分为2组，分别灌胃给药给予枸橼酸莫沙必利分散片粉末或胃漂浮缓释微丸，测定莫沙必利的血浆药物浓度，评价枸橼酸莫沙必利胃漂浮缓释微丸给药后的相对生物利用度。结果：本方法大鼠血浆中莫沙必利浓度的线性范围为0.2~40 ng·mL^-1 （r²=0.998 8）；日内及日间精密度RSD均小于15%。单剂量口服灌胃给药给予枸橼酸莫沙必利分散片粉末或胃漂浮缓释微丸0.2 mg （以枸橼酸莫沙必利计算）后，血浆中莫沙必利的C_max分别为（8.00±0.91），（6.85±0.68）ng·mL^-1；AUC_0→t分别为（7.01±0.73），（47.32±7.97）ng·h·mL^-1，AUC_0→∞分别为（7.59±0.90），（51.83±10.13）ng·h·mL^-1。以AUC_0→t和AUC_0→∞计算，枸橼酸莫沙必利胃漂浮缓释微丸的相对生物利用度分别为675%和683%。结论：将枸橼酸莫沙必利制成胃漂浮缓释微丸后，可显著提高其口服生物利用度。

Oral bioavailability of mosapride citrate gastric floating sustained-release pellets in rats

OBJECTIVE To establish a HPLC-MS/MS method to determine the concentration of mosapride in rat plasma and study the oral relative bioavailability of mosapride citrate gastric floating sustained-release pellets in rats after oral adminstration.METHODS rats were divided into two groups according to the random number table method, and mosapride citrate dispersible tablets powder or gastric floating sustained-release pellets were administered by gavage respectively. Then, the plasma drug concentration of mosapride was determined, and the relative bioavailability of mosapride citrate gastric floating sustained-release pellets after administration was evaluated.RESULTS The linear range of mosapride concentration in rat plasma was 0.240 ng·mL^-1 (r²=0.998 8) The intra-day and inter-day RSD were less than 15%. After oral administration of mosapride citrate dispersible tablet powder or gastric floating sustained-release pellets at a single dose of 0.2 mg (calculated by mosapride citrate), C_max of mosapride were (8.00±0.91),(6.85±0.68) ng·mL^-1, AUC_0→t (7.01±0.73),(47.32±7.97) ng·h·mL^-1, AUC_0→∞ (7.59±0.90),(51.83±10.13) ng·h·mL^-1, respectively. The relative bioavailability of mosapride citrate gastric floating sustained-release pellets in rats was 675% and 683% calculated with AUC_0→t and AUC_0→∞, respectively.CONCLUSION Mosapride citrate can be made into gastric floating sustained-release pellets, which can significantly improve its oral bioavailability.