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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 self-microemulsifying drug delivery system in rats. Methods: The establishment of high performance liquid chromatography, determination of midazolam and its active metabolite 1-hydroxy midazolam in plasma concentrations to investigate midazolam self-emulsifying microemulsion SD rats oral midazolam Pharmacokinetic parameters and bioavailability. Results: MDZ AUC0-∞ [(821.0 ± 157.2) μg.L-1.h and (362.4 ± 113.6) μg.L-1.h compared with commercial Dormicum (MDZ) , P <0.05], significantly reduced the ratio of 1’-hydroxy midazolam to midazolam AUC0-∞ (0.25 decreased to 0.14, P <0.05); MDZ self-microemulsification also significantly prolonged the MDZ in vivo MRT and t1 / 2 [MRT: (1.37 ± 0.15) h and (0.63 ± 0.13) h; t1 / 2: (0.7 ± 0.6) h and (0.330.11) h, P <0.05]. The oral bioavailability Dormicum (2.27 times of tablet) .Conclusion: Midazolam self-emulsifying microemulsion can effectively avoid the first pass effect of drugs on liver and gastrointestinal tract, and significantly improve the oral bioavailability of the drug.