WHO原料药预认证程序解析

目的为中国原料药进入国际市场找出一条合适的途径。方法查阅近年来相关文献,对WHO原料药预认证程序进行分析,阐述WHO原料药预认证的重要性。结果与结论深入学习国际组织相关法规,严格按照WHO GMP规范指导生产,接受WHO文档评估和现场检查,是中国原料药参与WHO国际采购、进入国际市场的最佳途径。     

头孢丙烯治疗急性细菌性下呼吸道感染的临床疗效评价

目的 :评价头孢丙烯治疗急性细菌性下呼吸道感染的临床有效性、安全性。方法 :轻、中度急性细菌性下呼吸道感染病人 115例随机分成 2组 ,头孢丙烯组 5 8例 (男性 37例 ,女性 2 1例 ;年龄 4 7a±s 13a)予头孢丙烯 5 0 0mg ,po ,bid ;头孢克洛组5 7例 (男性 34例 ,女性 2 3例 ;年龄 4 9a± 12a)予头孢克洛 5 0 0mg ,po ,tid。 2组均以 7～ 14d为一个疗程。结果 :头孢丙烯组与头孢克洛组的临床有效率分别为 93%与 91% (P >0 .0 5 ) ,细菌清除率为92 %与 89% (P >0 .0 5 ) ,2组均无明显不良反应。结论 :头孢丙烯可作为治疗轻、中度急性细菌性下呼吸道感染有效和安全的抗生素     

Coprocessing of Nevirapine and Stavudine by Spray Drying

The objective of the present study was to coprocess 2 active pharmaceutical ingredients (APIs), nevirapine (NVP) and stavudine (STV), by spray drying technique to overcome the respective problems of poor solubility and poor content uniformity. The coprocessed product (NVP-STV CP) and untreated APIs were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), particle size, surface area analysis, compressibility, and solubility. Coprocessing enhanced NVP solubility by ～1.5 fold and provided uniform distribution of low-dose STV in the formulation composite. Phase solubility studies elucidated the mechanism of enhanced NVP solubility. The coprocessed product was stable under accelerated stability conditions of 40°C/75% relative humidity (RH) for 3 months. The coprocessed product was formulated into 3 drug fixed dose combination (FDC) tablets with lamivudine (LMV), which gave an enhanced in vitro NVP drug release compared with the control formulation. Spray drying as a coprocessing technique optimally utilized the individual components of the antiretroviral FDC tablets and synergistically enhanced the performance attributes.     

头孢丙烯分散片在中国健康人体的药代动力学

目的研究头孢丙烯分散片在中国健康人体的药代动力学。方法 10名中国健康受试者,男女各半,单剂量口服头孢丙烯分散片500 mg。用高效液相色谱法同时测定血浆中顺式和反式头孢丙烯的浓度;用DAS 2.0药代动力学程序计算药代动力学参数。结果头孢丙烯的主要药代动力学参数:Cmax为(9.62±1.29)mg.L-1,Tmax为(1.30±0.35)h,t1/2(ke)为(1.32±0.15)h,V为(34.40±5.48)L,CL为(18.16±2.96)L.h-1,AUC0-10为(27.68±4.45)mg.h.L-1,AUC0-∞为(28.22±4.70)mg.h.L-1。结论头孢丙烯在人体内符合一级吸收的一室模型。     

头孢丙烯口腔崩解片的处方工艺及质量研究

目的:研究头孢丙烯口腔崩解片的处方工艺,并对其质量进行考察.方珐:将头孢丙烯与各辅料进行影响因素考察,选择合适辅料,单因素优化处方工艺,将制得的样品进行湿、热、光照影响因素实验和加速实验考察.结果:按优选处方制备的头孢丙烯口腔崩解片经加速实验考察,有关物质含量＜1％,在水中30 min的累积溶出度＞85％.结论:本研究制备的头孢丙烯口腔崩解片质量稳定,适合进一步开发.     

高效液相色谱法测定头孢丙烯中的有关物质

目的:建立高效液相色谱法同时测定头孢丙烯中的有关物质。方法:采用反相高效液相色谱法,固定相为十八烷基硅烷键合硅胶,以乙腈-0.05 mol·L-1磷酸二氢铵溶液(5:95,用磷酸调pH至4.4)为流动相,流速为1.0 mL·min-1,检测波长225nm。结果:PGOH、PGOH ESTER、头孢羟氨苄、7-PACA顺式异构体和7-PACA反式异构体最低检测限分别为0.1,0.1,0.1,0.5,0-μg·mL-1;平均加样回收率分别为98％,102％,101％,96％,95％。结论:该方法简便、快速,可一次性测定头孢丙烯中的有关物质。     

Simultaneous High-Performance Liquid Chromatographic Analysis of Cefprozil Diastereomers in a Pharmacokinetic Study

Cefprozil, a new oral cephalosporin, consists of a 90:10 cis:trans isomer mixture. Sensitive, specific and reproducible high performance liquid chromatographic methods have been developed for the simultaneous quantification of the two stereoisomers of cefprozil in plasma and urine samples from human and rats. Cephalexin acted as the internal standard. Plasma protein was precipitated with acetonitrile and trichloracetic acid with subsequent extraction of acetonitrile. After vortexing and centrifuging, the aqueous phase was injected onto a reverse phase C8 column. Urine samples were acidified with sodium acetate buffer (pH 3.8) and then directly injected onto a reverse phase C18 column. The detector was set at 280 nm. These methods were applied to determine protein binding of both isomers in human and rat sera, and to perform a pharmacokinetic study in human. Results showed that both isomers bound moderately to serum proteins with no interference by the other isomer. The pharmacokinetic study in human indicated that cefprozil was well absorbed and the cis and trans isomers have similar pharmacokinetics.     

头孢丙烯在健康志愿者和呼吸系统感染患者的药物动力学

目的:比较健康志愿者和呼吸系统感染患者po头孢丙烯的药物动力学.方法:用HPLC法测定10例健康志愿者和10例呼吸系统感染患者单次及多次po头孢丙烯500mg后的血药浓度,数据用PKBP-N1药物动力学模拟系统处理.结果:药-时曲线符合二室开放模型.单次给药后,健康组和患者组的T_(max)分别为1.43和1.46h,C_(max)分别达9.52和9.66μg/ml.T_(1/2β)分别为1.18和1.31h.经t检验两组间无显著性差异.连续给药7d,各组内d1与d7、组间d1与d7相比较,药物动力学参数无显著性差异.结论:头孢丙烯在体内无明显蓄积现象.     

国产头孢丙烯颗粒剂人体药代动力学和生物等效性研究

目的建立HPLC-UV法同时测定人血浆中的顺式和反式头孢丙烯,对国产头孢丙烯颗粒剂和胶囊剂进行人体药代动力学研究和人体相对生物等效性研究。方法将20名健康志愿者分两组进行单剂量双交叉试验,剂量均为500mg,两次试验间隔时间为7d。血浆样品用20%的三氯醋酸沉淀蛋白后,用乙腈和二氯甲烷的混合溶剂提取内源性杂质,离心后取上清液进样分析;色谱柱为Lichrospher C8柱(5μm,4.6mm×30cm),流动相为乙腈-1.5%的乙酸水溶液(1585),流速1.0ml·min-1,检测波长280nm,柱温为30℃,内标为头孢拉定。结果血浆中杂质不干扰样品的测定,标准曲线范围为0.0209~10.47mg·L-1,线性关系良好(r=0.9993),最低定量限为0.0209mg·L-1;参比制剂与受试制剂的达峰时间分别为1.7±0.3h,1.8±0.2h;达峰浓度分别为4.45±1.25mg·L-1、4.88±1.08mg·L-1,生物半衰期分别为1.89±0.45h和1.79±0.39h,用梯形法计算所得的AUC0-12分别为12.11±2.62mg·L-1·h-1、12.34±2.93mg·L-1·h-1,头孢丙烯受试制剂的相对生物利用度为(101.9±8.8)%。结论本分析方法操作简便,结果准确可靠。对Cmax、AUC0-12经对数转换,方差分析后进行双单侧检验及90%可信限判断,两制剂具有生物等效性。     

头孢克洛缓释片与头孢丙烯片对照治疗慢性支气管炎急性发作

目的: 比较头孢克洛缓释片与头孢丙烯片治疗慢性支气管炎急性发作(AECB)的有效性和安全性。方法:多中心随机单盲平行对照设计。缓释头孢克洛组予头孢克洛缓释片750mg,bid;头孢丙烯组予头孢丙烯500mg,bid,疗程均为7d。结果:202例AECB病人入选,缓释头孢克洛组102例,头孢丙烯组100例。治疗前2组基础情况、症状、体征和峰流速均具可比性。治疗后按意向性分析(ITT)和按方案分析(PP)缓释头孢克洛组和头孢丙烯组的临床有效率分别为84. 0 %, 74. 5 %和85. 4 %,74. 7 %,细菌学清除率分别为83 %和79 %, 2组间比较差别无显著意义(P>0. 05 );不良事件发生率缓释头孢克洛组7. 8 %,头孢丙烯组为6. 0 %, 2组比较差别无显著意义(P>0. 05)。结论:AECB病人应用头孢克洛缓释片750mg,bid,连续7d治疗,疗效确切,不良反应发生率低,与头孢丙烯相仿。