基于生物等效性分析呋塞米片体内外试验的相关性

Analysis of in Vitro-in Vivo Correlation of Furosemide Tablets Based on Bioequivalency

关键词:  呋塞米片  药物溶出度  生物等效性  体内外相关性

Key words:  Furosemide tablet  drug dissolution  bioequivalence  in vitro-in vivo correlation

摘要:

目的 开展体内外相关性试验以探讨国内生产的呋塞米片的药物溶出度试验是否可以替代生物等效性试验。方法 选择呋塞米片受试与对照制剂，按照中国药典要求和光纤药物溶出度实时测定仪测试方法，监测呋塞米累积溶出百分率并计算f₂相似因子，测定2种制剂的体内血药浓度并计算药动学参数，测算其体内吸收分数、生物利用度和生物等效性，分析呋塞米片体内外试验的相关性。结果 经f₂相似因子方法评估，受试与对照制剂的呋塞米溶出曲线相似，2种制剂的主要药动学参数t_max、C_max、AUC_0-24和AUC_0-∞、生物利用度和生物等效性均差异明显，其体内百分吸收系数和体内外试验的相关性较差。结论 国内生产的呋塞米片的药物溶出度试验尚不能替代生物等效性试验。

Abstract:

OBJECTIVE To do the test of in vitro-in vivo correlation(IVIVC) for discussing whether or not drug dissolution test of Furosemide tablets produced in the domestic could be replaced by bioequivalency(BE). METHODS The tested and control preparations of furosemide were selected. According to methods of requirements of the Chinese Pharmacopoeia 2015 and monitoring of fiber-optic in site dissolution testing equipment, the percent of accumulation furosemide dissolution were monitored and similar factor f₂ were calculated. The blood drug concentration of tested and control dosage forms in vivo were determined and the pharmacokinetic parameters were counted. The percent of absorption, bioavailability(BA) and BE were measured. IVIVC of Furosemide tablets was analyzed. RESULTS Two furosemide dissolution curves of tested and control preparations were similar by the way of similar factor f₂ evaluation. The differences of main pharmacokinetic parameters such as t_max, C_max, AUC_0-24 and AUC_0-∞, BA and BE between two preparations were significant. The discrepancy of the percent of absorption in vivo and IVIVC of Furosemide tablets were not significant. CONCLUSION The BE of Furosemide tablets produced in the domestic can't replaced by the drug dissolution test at present.