单硝酸异山梨酯缓释片的研究

 目的 研究试制的单硝酸异山梨酯缓释片(SRT)与德国麦克制药公司缓释胶囊(SRC)释放度、药代动力学、生物利用度。方法 采用高效液相色谱测定释放度、气相色谱测定12名健康志愿受试者在血中浓度变化情况，计算二者的药代动力学参数、相对生物利用度，并以双单侧 t 检验法进行统计分析。结果 两种缓释制剂的体外释放度符合一级动力学过程(SRT k=0.0716 h〈sup〉-1〈/sup〉,r=0.994；SRC:k=0.084 h〈sup〉-1〈/sup〉,r=0.997)；健康志愿者多剂量 po SRT及SRC，比较最低血药浓度，说明第3天已达稳态。稳态时两者之间血浆药物浓度波动指数(FI)及一个给药间隔内血浆药物浓度-时间曲线下的面积(AUC)均无显著差异(P＞0.05)，相对生物利用度为(105.45±11.10)%。结论 SRT与SRC是生物等效制剂。

Studies on sustained-release tablet of isosorbide-5-mononitrate

OBJECTIVE To study the dissolution,pharmacokinetics,relative bioavailability of the sustained release tablets(SRT)iv vitro and vivo.The reference was 5 monoretard-ratiopharm 40 (SRC,Merckle GmbH,Germany). METHODS The isosorbide-5-mononitrate (5-ISMN) in vivo was determined by HPLC.The 5-ISMN was determined after taking a single and multiple oral doses of SRT and SRC to 12 volunteers in an open randomized cross-over test.5-ISMN concentration in serum was assayed by GC method. RESULT The studies showed the SRT and SRC released drug with a first-order kinetics in vitro(SRT,k=0.0716 h^-1,r=0.994;SRC,k=0.084 h^-1,r=0.997).The steady-state status,based on through plasma concentration on day 3～6,was achieved on day 3.The drug fluctuation index (FI) of SRT and SRC in plasma and area under the plasma drug concentration-time curve for 0～24 h on day 6 of SRT and SRC were showed to be not significantly different(P＞0.05).The relative bioavailability was about (105.45±11.10)%. CONCLUSION The result of statistical analysis showed that the two formulations were bioequivalent.