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。     

长半衰期药物无清洗期时的生物等效性研究*

摘要目的：探讨长半衰期药物（t1/2>24 h）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。     

内源性药物生物等效性试验的问题与对策

本文综述了内源性药物生物等效性试验常见的一些问题,如测定准确度、内源性物质基线水平差异、自身反馈调节等,并探讨了这些问题的解决对策。     

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。     

On Assessment of Bioequivalence for Drugs with Negligible Plasma Levels

In bioavailability studies, bioequivalence between drug products is usually determined based on some pharmacokinetic responses such as area under the blood or plasma concentration-time curve and maximum concentration. For some drug products, however, we may have negligible plasma levels because their intended routes of administration. In this case, assessment of bioequivalence between drug products of this kind may be established using clinical endpoints such as therapeutic response and time to the onset of a therapeutic response. In this paper, we propose two procedures which modify the method of generalized estimating equations (Liang and Zeger, 1986) and the proportional hazard models for paired failure times to assess bioequivalence between two drug products under the structure of a standard two-sequence, two-period crossover design. An example concerning a bioequivalence trial for albuterol metered dose inhaler indicated for acute bronchospasm (Herson, 1991) is used to illustrate the proposed procedures.     

The Total Least Squares Method in Individual Bioequivalence Evaluation

We propose a simple method for comparison of series of matched observations. While in all our examples we address “individual bioequivalence” (IBE), which is the subject of much discussion in pharmaceutical statistics, the methodology can be applied to a wide class of cross‐over experiments, including cross‐over imaging. From the statistical point of view the considered models belong to the class of the “error‐in‐variables” models. In computational statistics the corresponding optimization method is referred to as the “least squares distance” and the “total least squares” method. The derived confidence regions for both intercept and slope provide the basis for formulation of the IBE criteria and methods for its assessing. Simple simulations show that the proposed approach is very intuitive and transparent, and, at the same time, has a solid statistical and computational background.     

A Two-stage Procedure with Controlled Error Probabilities for Testing Bioequivalence

The procedures currently used for testing the bioequivalence of two drug formulations achieve control over the error probability of erroneously accepting bioequivalence or over the probability of erroneous rejection, but not over both error probabilities. A two-stage procedure that rectifies this drawback is presented, assuming that the performance of the drug is characterized by a normally distributed variate.     

新型冠状病毒抗原快速检测研发现状及展望*

新型冠状病毒肺炎疫情的全球大流行,对全球公共健康、社会和经济运转造成了重大影响。在药物研发迟滞及疫苗有效性未得到充分验证的情况下,对人群进行大规模的快速筛查,寻找潜在的感染者(尤其是轻症和无症状患者),并进行集中隔离,切断传播途径和保护易感人群是首要的任务。因此对于SARS-CoV-2感染,早期诊断尤为重要。总结现有市场上的新冠病毒抗原快速检测产品,对全球抗原快速检测市场进行分析,概述其研发的动向并展望了我国在新冠抗原检测新方法、新技术方面的自主创新能力。     

Legal Liability to Volunteers in Testing New Drugs

Scientists test new drugs by giving them to volunteers. In spite of every precaution, the drug may harm the volunteer. Under Canadian law, can he recover damages against any of the persons connected with the test? He cannot succeed against the scientist if the latter had made complete disclosure of the risks and had then obtained the volunteer''s free consent. Where the subject of a test is a child or one of unsound mind, the guardian''s consent probably does not protect the scientist from a possible claim by the subject. Where a married woman is a volunteer, her husband''s consent is unnecessary. The volunteer cannot succeed against his family physician who referred him to the scientist unless the physician took an active part in an experiment that was conducted negligently or without a proper consent. The volunteer cannot succeed against the maker unless he has negligently prepared the drug or given misleading information.