药物临床试验质量控制浅析

目的:建立有效的药物临床试验质量控制体系。方法:结合笔者多年的临床研究工作管理经验,对药物临床试验质量的关键环节和控制措施进行探讨并提出建议。结果与结论:药物临床试验质量控制的关键环节在于建立完善的组织管理体系、建立健全规章制度和科学规范的标准操作规程、严格执行《药物临床试验质量管理规范》和现行法规等,采取建立药物临床试验监查员准入制度、三级质控制度、临床数据电子化管理、药物临床试验申报平台、临床研究协调员制度等控制措施,以全面保证药物临床试验的质量。     

关于实施药品临床试验管理规范的探讨

临床试验是新药开发不可缺少的环节。临床试验中遵循药品临床试验管理规范（GCP）的原则有助于保护受试者的合江权益及健康安全，并确保临床试验结果科学可靠，本文对我国目前药品临床试验实施GCP的现状及解决问题的对策作了一些探讨。     

Plackett-Burman联用正交设计优选干蟾皮总生物碱纯化工艺

目的:运用Plackett-Burman实验设计联用正交实验考察各影响因素显著性,筛选出干蟾皮吲哚类生物碱纯化最佳工艺,为其开发与应用提供依据。方法:运用Plackett-Burman实验设计筛选主要影响因素,采用正交试验优选干蟾皮总生物碱富集工艺。以乙醇浓度、乙醇用量、洗脱流速为考察因素,生物碱含量为考察指标,利用正交试验优选最佳工艺,并进行验证分析。结果:干蟾皮吲哚类生物碱的最佳纯化工艺为:6BV的90%乙醇在洗脱流速为4ml·min-1条件下富集纯化,吲哚类生物碱含量为5.21%,浸膏收率为3.45%。结论:利用Plackett-Burman实验设计联用正交试验确定了干蟾皮总生物碱的纯化工艺,该方法稳定,简便易行。     

我院临床医师临床试验管理规范培训的经验介绍

目的提高本院临床试验质量及临床医师的临床试验管理规范（GCP）意识。方法我院通过选派骨干参加省级、国家级学习班,邀请相关科研单位及GCP资深专家等方式对我院临床医师进行培训。结果通过以上措施,提高了我院临床医师的GCP意识,确保了我院新药临床试验的质量。结论GCP是设计、实施、记录和报告设计人类对象参加的试验国际性伦理和科学质量标准,GCP培训是新药临床试验中的一个不可缺少的环节。     

试论我国实施中药GCP存在的问题及对策

本文概要分析了我国实施中药GCP存在的问题,提出了有效实施中药特色GCP的对策.     

Epstein-Barr virus-associated gastric carcinoma in the remnant stomach: de novo and metachronous gastric remnant carcinoma

Background The remnant stomach corresponds to the gastric cardia, but is exposed to a completely different environment. The present study was performed to investigate the role of Epstein-Barr virus (EBV) infection in patients with gastric remnant carcinoma (GRC).Methods Clinicopathological features, gastritis, and infection by EBV were investigated in patients with two types of GRC: GRC occurring at an interval of 10 years or longer between operations (de novo GRC group) and GRC occurring within 10 years after the initial operation for gastric carcinoma (metachronous GRC group).Results EBV involvement in the de novo GRC group (23%) was not significantly different from that in the cardia of non-remnant carcinomas (controls; 18%). EBV involvement showed greater correlations in male patients (18/63; 28%), and in those with gastritis cystica polyposa (GCP; 13/41; 31%), and those with an interval of 20 years or longer (15/50; 30%) than with the other parameters. Multivariate analysis showed a significant correlation between GCP and EBV infection. Histologically, hyperplasia or mild atrophy, and mild lymphocytic infiltration were observed in 56% and 67% of non-neoplastic mucosa of EBV-associated GRC, respectively. In the metachronous GRC group, EBV-encoded mRNA in situ hybridization (EBER-ISH) of 27 pairs of primary gastric carcinomas (GCs) and metachronous GRCs indicated that only six EBV (+) metachronous GRCs were derived from EBV (+) GC.Conclusions Epstein-Barr virus infection, together with long-standing inflammation, which causes GCP, may facilitate the development of de novo GRC. Close follow-up of patients treated with distal gastrectomy for EBV-associated GC is necessary to detect metachronous GRC.     

中药新药临床试验对照药选择的问题与对策

对照药的选择是中药新药临床试验过程中的一个重要环节，直接关系到，临床试验的质量，本归纳了目前中药临床试验过程中对照药选择的若干问题，并提出解决问题的对策和建议。     

新药临床试验中GCP实施的问题与对策

现阶段“药品临床试验管理规范”(GCP)的实施中存在诸多问题，笔者通过对新版GCP的学习，分析目前临床研究中存在的问题，并探讨相应的对策。且响应国际新形势下对GCP的要求，深切感受到现阶段我国药品临床研究中实施GCP的必要性和重要性。     

Detection of ECG effects of (2R,4R)-monatin,a sweet flavored isomer of a component first identified in the root bark of the Sclerochitin ilicifolius plant

Enzymatically-synthesized (2R,4R)-monatin has, due to its pure sweet taste, been evaluated for potential use in foods. Non-clinical studies have shown that (2R,4R)-monatin is well tolerated at high dietary concentrations, is not genotoxic/mutagenic, carcinogenic, or overtly toxic. In a pharmacokinetic and metabolism study involving 12 healthy males, consumption of a single oral dose (2 mg/kg) of (2R,4R)-monatin resulted in a small reduction of heart rate and prolongation of the QTcF interval of 20–24 ms, corresponding to the time of peak plasma levels (t_max). These findings were evaluated in a cross-over thorough QT/QTc study with single doses of 150 mg (2R,4R)-monatin, placebo and positive control (moxifloxacin) in 56 healthy males. Peak (2R,4R)-monatin plasma concentration (1720 ± 538 ng/mL) was reached at 3.1 h (mean t_max). The placebo-corrected, change-from-baseline QTcF (ΔΔQTcF) reached 25 ms three hours after dosing, with ΔΔQTcF of 23 ms at two and four hours. Using exposure response (QTc) analysis, a significant slope of the relationship between (2R,4R)-monatin plasma levels and ΔΔQTcF was demonstrated with a predicted mean QT effect of 0.016 ms per ng/mL. While similarly high plasma levels are unlikely to be achieved by consumption of (2R,4R)-monatin in foods, QTc prolongation at this level is a significant finding.