咪达唑仑自微乳化释药系统在大鼠体内的药动学  

Study on pharmacokinetics and bioavailability of midazolam self-microemulsifying drug delivery system in rats

作　　者：饶子超[1] 斯陆勤[1] 关延彬[1] 向道春[2] 裘军[1] 李高[1] 

机构地区：[1]华中科技大学同济医学院药学院药剂教研室,湖北武汉430030 [2]华中科技大学同济医学院附属同济医院药学部,湖北武汉430030

出　　处：《中国医院药学杂志》2010年第13期1084-1088,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金资助项目(编号:30873171)

摘　　要：目的:考察咪达唑仑自微乳化释药系统在大鼠体内的药动学性质与生物利用度。方法:建立高效液相色谱法,测定咪达唑仑及其活性代谢物1-羟基咪达唑仑在血浆中的浓度,考察咪达唑仑自乳化微乳对SD大鼠口服咪达唑仑药动学参数及生物利用度的影响。结果:与市售Dormicum(片剂相比,MDZ自微乳化制剂明显增加MDZ的AUC0-∞[(821.0±157.2)μg.L-1.h和(362.4±113.6)μg.L-1.h,P<0.05],显著降低1′-羟基咪达唑仑与咪达唑仑AUC0-∞的比值(0.25减少到0.14,P<0.05);MDZ自微乳化制剂还可显著延长MDZ在体内的MRT及t1/2[MRT:(1.37±0.15)h和(0.63±0.13)h;t1/2:(0.7±0.6)h和(0.330.11)h,P<0.05],口服生物利用度为Dormicum(片剂的2.27倍。结论:咪达唑仑自乳化微乳能有效避免肝脏及胃肠道对药物的首过效应,显著提高药物的口服生物利用度。OBJECTIVE To investigate the pharmacokinetics and bioavailability of midazolam （MDZ） self-microemulsifying drug delivery system in rats. METHODS An HPLC method was established to determine the concentration of MDZ and its metabolite 1 ＇-hydroxymidazolam （1 ＇-OHMDZ） in plasma. MDZ self-mieroemulsifying drug delivery system was prepared, and its pharmacokinetic parameters and bioavailability in SD rats were studied after oral administration. The concentration-time data were fitted using 3P97 pharmaeokinetics program and t-test was used to compare significant difference between pharmacokinetics parameters of the two groups. RESULTS The pharmacokinetic parameters showed that MDZ microemulsion significantly increased MDZ AUG0-∞[（821.0± 157. 2）μg·L^-1·h vs. （362. 4 ± 113. 6）μg·L^-1·h, P〈0. 05]） and inhibited the activity of CYP 3A by decreasing the ratio of AUG0-∞ （1 ＇ -OH MDZ）/AUC0-∞ （MDZ） in comparison to Dormicum （0. 14 vs. 0. 25, P〈 0. 05）. MRT and t1/2 of MDZ were obviously prolonged in MDZ microemulsion treated group compared with Dormieum group MRT： （1.37 ± 0. 15） h vs. （0. 63 ± 0. 13）h; t1/2 ： （0. 7 ± 0. 6） h vs. （0. 33 ± 0. 11 ） h, respectively, P〈0. 05）. The oral bioavailability of MDZ in microemulsion was 2. 27-fold higher than that of the commercial tablet. CONCLUSION It was found that the first-pass metabolism of MDZ could be avoided effectively with significantly increased bioavailability in rats after oral administration by MDZ self-microemulsifying drug delivery system.

关 键 词：咪达唑仑 细胞色素P4503A 自微乳化释药系统 药动学 

分 类 号：R969.1[医药卫生—药理学]