肾移植患者应用更昔洛韦后环孢菌素A的药动学及临床生化指标的研究

对１０例肾移植患者应用与未用更昔洛韦后环孢菌素Ａ的药动学参数及临床生化指标进行研究。采用荧光偏振免疫法测定血药浓度，３Ｐ８７程序拟合药动学参数。结果显示：应用更昔洛韦后，环孢菌素Ａ药动学参数Ｋｅ、ｔ１／２（Ｋａ）分别由未用组的（０．１６±０．０４）ｈ－１和（１．３９±０．７６）ｈ降至（０．０９±０．０５）ｈ－１和（０．５０±０．３２）ｈ（Ｐ＜０．０５），Ｔｍａｘ由（３．６７±０．７７）ｈ减至（２．００±０．７８）ｈ（Ｐ＜０．０１），ｔ１／２（Ｋｅ）由（４．０８±１．８５）ｈ增至（１０．５１±６．４２）ｈ（Ｐ＜０．０５），峰浓度Ｃｍａｘ平均升高２７％。肾移植后应用更昔洛韦组肾功指标下降，肝功指标上升，其中血清肌酐、总胆红质与未用组相比有统计学意义。表明更昔洛韦使肾移植患者环孢菌素Ａ的药动学参数及临床生化指标发生改变，提示临床调整用药方案。     

更昔洛韦防治肾移植术后CMV感染的对照研究

总结了更昔洛韦防治肾移植患者巨细胞病毒（Ｃｙｔｏｍｅｇａｌｏｖｉｒｕｓ，ＣＭＶ）感染的研究结果。预防研究共１５３例，更昔洛韦组８８例，阿昔洛韦组６５例。两组预防ＣＭＶ疾病的效果有明显差异（９．１％ｖｓ２４．６％，Ｐ＜０．０５），而预防ＣＭＶ活动性感染的效果无明显差异（２０．４％ｖｓ１５．６％，Ｐ＞０．０５），但更昔洛韦组ＣＭＶ活动性感染的持续时间明显短于阿昔洛韦组（２～６周ｖｓ３～９周，Ｐ＜０．０１）。治疗ＣＭＶ肺炎３１例，更昔洛韦组１５例治愈率８０％；阿昔洛韦组１６例治愈率２５％（Ｐ＜０．０５）。认为更昔洛韦能有效预防ＣＭＶ疾病，缩短活动性感染的持续时间，对ＣＭＶ疾病有比较满意的治疗效果。     

Analysis of ganciclovir and its related substances using high performance liquid chromatography and liquid chromatography-mass spectrometry methods

Objective High performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC/MS) methods were developed for the determination of ganciclovir and its related substances. Methods A Hypersil ODS2 column (4.6mm×250mm, 5μm) was used with a mobile phase of 0.02M potassium 1.0mL/min, and UV detector set at 254nm was used for monitoring the eluents. Results The method was simple, rapid, selective and capable of separating all related substances at trace level with a detection limit of 0.04μg/mL. It has been validated with respect to accuracy, precision, linearity, and limits of detection and quantification. The linearity range was 10.2-153.0μg/mL with r=0.9998. The percentage recoveries ranged from 96.7% to 101.6%, and RSD was 1.24%-1.96% (n=5). Conclusion The method was found to be suitable not only for monitoring the reactions during the process development but also for quality control of ganciclovir. For identification of related substances, LC/MS was used. The mainly related substances of ganciclovir active pharmaceutical ingredients (API) were determined as guanine, (1, 3-dioxolan-4-yl) methyl acetate, and diacetyl guanine.     

RP-HPLC法测定更昔洛韦血清浓度

为建立 HPL C法测定更昔洛韦血药浓度的方法。采用反相高效液相色谱法 ,以阿昔洛韦为内标 ,流动相为甲醇水溶液 (5∶ 95) ,检测波长为 2 52 nm。结果在 0 .2～ 15μg· ml-1范围内呈良好的线性关系。方法平均回收率为 10 0 .52 % ,RSD日内为 2 .7% ,日间为 2 .5%。说明本方法灵敏度高 ,适合于更昔洛韦的血药浓度测定及药代动力学研究。