为寻找新的大豆异黄酮前药，采用建立的生物样品中药物浓度测定的液相色谱法对新型大豆异黄酮染料木素磺酸酯（GBS）进行前药判定以及大鼠体内药物动力学研究，以考察前药中染料木素（GE）的口服相对生物利用度是否改善。在大鼠体内药物代谢实验中，灌胃给予的大鼠血浆中能检测到GE的存在。在临床前药物动力学实验中，该前体药以40mg／kgGE在大鼠体内的动力学过程符合一室模型。GBS中GE的相对口服生物利用度为原药的198．6％。结果表明：相对于原药GE，前药中GE的相对口服生物利用度得到极大地改善。该前药有进一步研究的意义。

The oral bioavailability of genistein (GE) in its benzensulfonate prodrug was studied in search for its novel prodrug.The plasmas were collected at different points of time after the intragastric or intravenous administration of genistein benzensulfonate (GBS) 40 mg/kg to rats.The GBS and GE contents in plasma were determined by HPLC.The compartment model was fitted and pharma cokinetic parameters were calculated by DAS 2.1.1.The results indicated that the dynamic processes of GE were consistent with two compartment model after intragastric administration of GBS prodrug to rats.The relative oral bioavailability of GE in prodrug GBS was 198.6％.In conclusion,the above results demonstrated that the oral bioavailability of GE in prodrug had been improved remarkably.

目的探讨熊果酸分别口服、静脉注射及合用环孢素后,其药代动力学变化。方法将15只SD雄性大鼠按随机数字表法分为3组,每组5只。口服给药组予80 mg·kg-1的熊果酸灌胃;合用环孢素组先予10 mg·kg-1环孢素灌胃,15 min后再灌服80 mg·kg-1的熊果酸;尾静脉给药组予熊果酸原料药(80 mg·kg-1,先用少量的DMSO溶一下,再用生理盐水稀释)尾部静脉注射。采用HPLC方法测定血药浓度,DAS软件分析药代动力学参数。结果与口服给药组相比较,合用环孢素组及静脉给药组其各药代动力学参数AUC(0-t)、AUC(0-∞)及Cmax均显著增大(P0.05)。结论口服给药后熊果酸在大鼠体内的生物利用度较低;环孢素可增加熊果酸的口服生物利用度。

Objective To explore the changes in pharmacokinetics of ursolic acid after oral ad-ministration,intravenous injection or combined treatment with cyclosporine.Methods Fifteen male SD rats were randomly divided into three groups,with 5 rats in each group.The oral admin-istration group was intragastrically given ursolic acid 80 mg·kg -1 .The intravenous administra-tion group was injected with ursolic acid 80 mg·kg-1 via tail vein (ursolic acid was dissolved in DMSO and then diluted in normal saline).The combined treatment group was intragastrically giv-en ursolic acid 80 mg· kg-1 15 minutes after treatment with cyclosporine 10 mg· kg-1 .Blood concentrations of ursolic acid were determined by HPLC,and pharmacokinetic parameters were analyzed using DAS software.Results Compared with oral administration group,pharmacokinet-ics parameters AUC(0-t),AUC(0-∞) and Cmax increased significantly in both intravenous adminis-tration group and combined treatment group.Conclusion The bioa

建立高效液相色谱-质谱联用法(LC-MS/MS)测定大鼠灌胃给药的生物利用度.大鼠随机分为2组,分别尾静脉和灌胃给予100mg·kg-1木通皂苷D,于不同时间点眼眶取血,用LC-MS/MS法检测血浆中药物质量浓度,计算大鼠灌胃给药的生物利用度.结果表明:木通皂苷D线性范围为10~1 000ng·mL-1,最低定量限为10ng·mL-1.准确度与精密度试验结果显示方法日间、日内变异均小于15%,相对偏差为-2.8%~4.6%,低、中、高3个质量浓度提取回收率为95.3%~108.1%.静脉组和口服组的药时曲线下面积AUC0-INF分别为(231 725.98±46 527.21)和(383.63±54.62)ng·h·mL-1,灌胃给药的绝对生物利用度为0.13%.表明木通皂苷D大鼠灌胃给药生物利用度很低.

A LC-MS/MS method was used to determine oral bioavailability of akebia saponin D in rat.SD rats were randomly divided into two groups.Dose of 100 mg·kg-1 akebia saponin D was given by stomach tube or by caudal vein inj ection.Blood samples were collected at different time intervals after administration through orbit vein.Plasma drug concentration was detected by LC-MS/MS,oral bioavailability was then calculated. The LC-MS/MS assay calibration curve was linear over the range of 10~1 000 ng·mL-1 .Intra-and inter-day variations were both less than 1 5%.Relative deviation was from -2.8%~4.6%.Recoveries of akebia saponin D were from 95.3%~108.1%.AUC0-INF in injection group and oral group were (231 725.98±46 527.21)and (383.63±54.62)ng·h·mL-1 respectively.Absolute bioavailability for intragastric administration was 0.13%. Bioavailability of akebia saponin D by intragastric administration was very low.

目的对新近发展的固体自微乳化给药系统(S-SMEDDS)文献进行综述。方法查阅近年国内外相关文献并进行归纳和总结。结果对固体自微乳的载体、固化技术以及缓控释制剂进行了探讨,为研究水难溶性药物的生物利用度及适合药物释放特性的S-SMEDDS技术提供相关参考。结论固体自微乳化系统可以显著提高难溶性药物的口服生物利用度,且兼顾了液态自微乳和固体制剂二者的优势,是一个极具潜力的新型制剂。

Objective To review the newly developed solid self-microemulsifying drug delivery system (S-SMEDDS).Meth-ods Relevant literatures at home and abroad in recent years were consulted and summarized .Results Solid self-microemulsions car-rier, solidification technology and controlled release formulations were discussed , in order to provide relevant references for improving the bioavailability of water-insoluble drugs and the SMEDDS technology for drug release characteristics .Conclusion The utilization of the solid self-emulsifying drug delivery system could significantly enhance the oral bioavailability of water -insoluble drugs .As a new formulation, S-SMEDDS presented huge potential .

目的：：研究瑞舒伐他汀钙胶囊和片剂在健康人体内的药动学过程和相对生物利用度。方法：健康志愿者24名,随机双交叉单剂量口服瑞舒伐他汀钙胶囊(受试制剂)和瑞舒伐他汀钙片(参比制剂),剂量均为20 mg,采用HPLC-MS/MS测定血浆中瑞舒伐他汀钙的浓度,用DAS 3.0药动学程序计算药动学参数和生物利用度,并进行生物等效性评价。结果：单剂量口服瑞舒伐他汀钙受试和参比制剂后,血浆瑞舒伐他汀的tmax分别为(3.56±1.68) h和(3.63±1.56) h；Cmax分别为(21.17±13.74) ng·ml-1和(26.33±23.22) ng·ml-1；t1/2分别为(10.68±5.50) h 和(9.04±6.00) h；AUC0-t分别为(219.31±146.09) ng·h·ml-1和(252.43±194.96) ng·h·ml-1；AUC0-∞分别为(225.32±146.76) ng·h·ml-1和(257.24±194.61) ng·h·ml-1, AUC0-t、AUC0-∞和Cmax的90%置信区间分别为81.1%~106%,81.8%~105.4%和77.9%~104.5%。受试制剂的相对生物利用度F为(100.7 ± 54.1)%。结论：瑞舒伐他汀钙受试制剂与参比制剂具有生物等效性。

Objective:To develop an HPLC-MS/MS method for the determination of rosuvastatin in plasma and study the relative bioavailability and bioequivalence of the capsules and tablets in Chinese healthy volunteers. Methods: A single oral dose (20 mg of the test or reference preparation) was given to 24 male healthy volunteers in a randomized crossover study. The plasma concentration of rosuvastatin was determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated and the bioavailability and bioequiva-lence of the two preparations were evaluated by DAS 3. 0 software. Results:After a single dose, the pharmacokinetic parameters of ro-suvastatin capsules and tablets were as follows:Tmax was (3. 56 ± 1. 68) h and (3. 63 ± 1. 56) h, Cmax was (21. 17 ± 13. 74) ng· ml-1 and (26.33 ±23.22) ng·ml-1, t1/2 was (10.68 ±5.50) h and (9.04 ±6.00) h, AUC0-t was (219.31 ±146.09) ng·h· ml-1 and (252. 43 ± 194. 96) ng·h·ml-1 , AUC0-∞ was (225. 32 ± 146. 76) ng·h·ml-1 and (25