长半衰期药物无清洗期时的生物等效性研究

目的：探讨长半衰期药物（t1／2〉24h）在无清洗期时生物等效性研究中的AUC和Cmax的计算,通过无清洗期的实验数据推算出正常清洗期的数据。方法：利用SPSS软件,建立二室模型口服药物在无清洗期时的半衰期为100小时的生物等效性模型,通过优化AUC和Cmax的计算方法,降低药物残留对第二周期药物浓度的影响,进而增加AUC和Cmax的计算的精确性,最后用较精确的方法推算出正常清洗期的AUC和Cmax,利用精确的数据进行生物等效性的进一步验证。结果：在无清洗期的状态下,取样时间在大于0．8个半衰期时,平均值法计算的Auc和Cmax的结果误差小于5％,变异系数小于25％,较为精确,生物等效性研究进一步验证了这一观点。结论：在无清洗期的情况下,生物等效性研究最小的采样时间为0．8个半衰期。     

孟鲁斯特钠咀嚼片在健康人体内药动学和生物等效性

目的:研究两种(仿制新药与市售)孟鲁司特钠咀嚼片在人体内生物等效性。方法:采用单中心、随机、开放、双周期自身交叉试验设计,20名健康男性志愿者分2周期分别口服受试制剂和参比制剂各10 mg,HPLC法测定血浆中孟鲁司特钠咀嚼片的浓度,用DAS2.1.1软件计算人体药动学参数并进行生物等效性评价。结果:受试制剂和参比制剂两药的主要药代动力学参数AUC0-t分别为(17.94±6.19)μg h/ml和(17.37±4.73)μg h/ml,AUC0-∞分别为(18.26±6.16)μg h/ml和(17.64±4.66)μg h/ml,Cmax分别为(5.58±1.95)μg/ml和(5.54±1.65)μg/ml,Tmax分别为(2.03±0.97)h和(1.93±0.69)h,t1/2分别为(1.20±0.17)h和(1.19±0.13)h。受试制剂的平均相对生物利用度为(101.5±6.56)%。结论:受试制剂和参比制剂具有生物等效性。     

头孢氨苄胶囊制剂人体生物等效性研究

目的:研究新仿制的头孢羟氨苄胶囊制剂与市场在售的同类制剂在健康人体内的生物等效性。方法:采用随机交叉试验设计,20名健康男性志愿者分别口服受试制剂与参比制剂500 mg,HPLC法测定血浆中头孢氨苄的浓度,用DAS 2.0软件计算药动学参数并进行生物等效性评价。结果:受试制剂和参比制剂两药的主要药代动力学参数,Cmax分别为(18.12±3.17)μg/ml和(21.28±3.77)μg/ml,Tmax分别为(1.09±0.37)h和(1.04±0.33)h,t1/2分别为(1.15±0.22)h和(1.14±0.20)h,AUC0-t分别为(35.43±5.39)μg h/ml和(37.27±4.76)μg h/ml,AUC0-∞分别为(36.68±6.06)μg h/ml和(38.62±5.48)μg h/ml,受试制剂的平均相对生物利用度为(96.50±7.2)%。结论:受试制剂和参比制剂具有良好的生物等效性。     

妇宁康泡腾胶囊的药代动力学研究

目的研究妇宁康泡腾胶囊在家兔体内的药动学特点。方法用HPLC法测定甘草酸在家兔体内48 h血药浓度,采用3P87药动学程序计算药动学参数。结果主要药动学参数为t1/2=8.956 h,Tmax=8.27 h,Cmax=0.4544μg/ml,AUC=37.161。结论该制剂在家兔体内吸收代谢缓慢,其生物半衰期超过8 h。     

TOST法评价药物生物等效性的研究进展

自20世纪末以来,随着药物制剂的改变,出于保护公众健康的需要,生物等效性得到迅速发展,成为众多出版物的热门话题.本综述描述了这方面的国际规则和历史,为生物等效性双单侧检验的主要步骤提供了一个大纲,介绍了生物等效性检验中所使用的部分研究设计和分析方法,其中包括两期设计和多于两期设计.随着新的以TOST为基础的评价方法的出现和应用,药物生物等效性的评价也将更加准确合理.     

生物仿制药现状与发展趋势分析

生物仿制药是指原研生物药物在专利保护到期后,其他企业利用已有的数据进行简化生产并被批准上市的、与原研药物在结构和质量上非常相似、具有相当的生物活性和生物等效性的生物制药产品。相比于化学药,生物药通常分子量大且结构复杂,因而生物药的仿制往往难度较大,是系统工程,涉及的靶点选择、工程菌的构建、培养基的筛选、大规模培养体系的建立、分离纯化体系的建立、药物后修饰等诸多环节均有较高的技术壁垒;加上生物仿制药在审批过程中不仅需要临床Ⅰ期的药效和药代动力学试验来证明生物等效性外,还需要临床Ⅲ期试验来证明生物仿制药大范围使用后的疗效、不良反应、药物间的相互作用等,因此生物仿制药的研发成本较化学仿制药高,研发周期和审批周期也相对较长。     

我国仿制药人体生物等效性临床试验研究室建设的现状与发展路径

我国开展仿制药一致性评价最主要的困难之一是临床试验资源不足,解决办法是考虑将生物等效性临床试验资格认定调整为备案 管理。因此,对备案的医疗机构建设生物等效性试验研究室是一个潜在的挑战。文章分析了国内当前具备生物等效性 / I期临床资质的 机构、分布、承担项目能力及生物等效性临床试验机构、药物分析实验室和合同研究组织之间的关系等,对仿制药生物等效性临床试验 研究室的建设内容和规模展开讨论,供业内及监管部门参考。     

基于多组学数据的肿瘤药物敏感性预测北大核心CSCD

肿瘤药物敏感性预测在指导患者临床用药方面具有重要意义。本文基于癌症药物敏感性基因组学数据库(genomics of drug sensitivity in cancer, GDSC) 198种药物的细胞系敏感性IC50数据,通过Stacking集成学习构建了包含基因表达、基因突变、拷贝数变异数据的多组学癌症药物敏感性预测模型。采用多种特征选择方法对基因特征进行降维,使用Stacking方法集成6种初级学习器和1种次级学习器进行建模,采用5折交叉进行模型验证。预测结果中AUC大于0.9的占比为36.4%,在0.8–0.9之间的占比为49.0%,最低AUC为0.682。基于Stacking构建的多组学预测模型较已有单组学和多组学模型的准确性和稳定性具有优势。多组学整合预测药物敏感性优于单一组学。特征基因功能注释和富集分析解析了肿瘤对sorafenib潜在的耐药机制,从生物学角度提供了模型可解释性及其应用于临床用药指导的价值。     

不同水温和给药方式下磺胺甲(口恶)唑在草鱼体内的药动学研究

在18℃和28℃的不同水温条件下,分别采用口灌和腹腔注射的给药方式,给予草鱼100mg/kg体重单剂量的磺胺甲(口恶)唑(SMZ),以HPLC法测定草鱼血浆和肌肉中药物浓度,用MCPKP药代动力学软件处理药时数据,结果表明,18℃条件下,草鱼口灌SMZ的分布半衰期T1/2α、消除半衰期T1/2β、达峰时间Tp均显著长于28℃(P＜0.01),其峰浓度Cmax显著低于28℃下的值(P＜0.01);腹腔注射给药时,SMZ在鱼体血浆和肌肉中的吸收与分布较口服快,消除较口服也快.在水温18℃条件下,口灌SMZ在草鱼血浆中的药时数据符合带时滞的二室开放模型,腹腔注射的符合无时滞二室开放模型;水温28℃条件下,口灌SMZ在草鱼血浆中的药时数据符合可忽略时滞的二室开放模型.根据SMZ的药代动力学规律、最低有效血药浓度和抗菌药物应用的一般原则,制定了SMZ的用药方案:治疗温水性鱼类细菌性疾病,在水温18℃左右,口服或注射100mg/kg剂量的SMZ,以每天给药两次,3d一个疗程为宜;在水温28℃左右,以每天给药3-4次为宜.该项研究全面了解了在不同水温和不同给药方式下SMZ在鱼体内的药动学规律,为确定合理的临床用药方案以及无公害水产品中药物残留监测提供了可靠的理论依据.     

重组人血管内皮抑素在Beagle犬体内的药代动力学研究

研究重组人血管内皮抑素(rhEndostatin)静脉注射后在Beagle犬体内的药代动力学过程,为临床应用提供药代动力学数据。用酶联免疫吸附试验(ELISA)竞争法检测Beagle犬静脉注射rhEndostatin后不同时间的血药浓度,并将血药浓度-时间数据经计算机拟合,计算出相应参数。rhEndostatin静脉注射Beagle犬后,药物的分布半衰期平均为(0.34±0.04)h,消除半衰期为(16.5±1.6)h。血药浓度-时间曲线下面积(AUC)与剂量呈正相关,相关系数为0.999 9。血浆清除率(CLs)均值为(0.123±0.006)l/h,高、中、低剂量CLs基本相同。rhEndostatin在Beagle犬体内的药代动学过程基本符合线性药动学特征,血药浓度-时间曲线符合二房室模型。rhEndostatin在Beagle犬体内药代动力学过程的研究对其进一步开发具有指导价值。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.