High Sensitivity Detection of a Solubility Limiting Surface Transformation of Drug Particles by DNP SENS

We investigate the presence of a surface species for the active pharmaceutical ingredient (API) AZD9496 with dynamic nuclear polarization surface enhanced nuclear spectroscopy (DNP SENS). We show that using DNP we can elucidate the presence of an amorphous form of the API at the surface of crystalline particles of the salt form. The amorphous form of the API has distinguishable ¹³C chemical shifts when compared to the salt form under various acidic conditions. The predominant form in frozen particles of AZD9496 is the salt, and we provide evidence to suggest that the amorphous layer at the surface is mainly made up of the dissociated free form.     

难治性癌痛患者临床药学监护要点和实践

临床药师参与到难治性癌痛患者疼痛评估、药物重整、个体化镇痛方案制定、围术期用药监护、不良反应监测、患者及家属用药教育等过程,总结监护要点,构建药学监护服务模式,进行个体化药学服务,能有效提高治疗效果,体现了临床药师的价值,在临床实践中具有可操作性。     

阿得贝利单抗联合化疗一线治疗广泛期小细胞肺癌的成本效果分析

目的 从中国医疗卫生体系角度评价阿得贝利单抗联合化疗对比化疗一线治疗广泛期小细胞肺癌的成本效果。方法 采用CAPSTONE-1临床试验所获数据(阿得贝利单抗组230例,化疗组232例),建立马尔可夫模型模拟广泛期小细胞肺癌疾病过程。分别计算每组的总成本、质量调整生命年(quality-adjusted life-years,QALYs)、增量成本效果比(incremental cost-effectiveness ratio,ICER)。对关键参数进行敏感性分析。结果 与单纯化疗方案(依托泊苷联合卡铂)相比,在考虑慈善援助的情景下,阿得贝利单抗联合化疗的ICER为157128.79元·QALY^-1,在不考虑慈善援助的条件下,阿得贝利单抗联合化疗的ICER为351367.27元·QALY^-1。敏感性分析结果显示效用值和阿得贝利单抗的价格是主要的影响因素。结论 阿得贝利单抗联合化疗方案对比单纯化疗方案治疗广泛期小细胞肺癌在中国现有的经济水平下不具有成本效果优势;考虑慈善赠药时,阿得贝利单抗联合化疗方案具有成本效果优势的概率为44.5%。     

达可替尼对比吉非替尼一线治疗EGFR突变晚期或转移性非小细胞肺癌的成本效果分析

目的 比较达可替尼和吉非替尼一线治疗中国表皮生长因子受体(EGFR)突变晚期或转移性非小细胞肺癌(NSCLC)的成本效果.方法 建立无疾病进展、疾病进展和死亡三种健康状态的分区生存模型.基于ARCHER 1050临床试验获取转移概率和安全性数据,根据已发表文献获得健康效用值,从卫生服务体系角度只考虑直接医疗成本,包括药...     

Analyses of Direct and Indirect Impacts of a Positive List System on Pharmaceutical R&D Investments

Background

The South Korean government recently enacted a Positive List System (PLS) as a major change of the national formulary listing system and reimbursed prices for pharmaceutical products. Regardless of the primary goal of the PLS, its implementation might have spillover effects by influencing the pharmaceutical industry’s research and development (R&D), potentially leading to a variety of responses by firms in relation to their R&D activities.

Objective

We investigated the spillover effect of the PLS on R&D investments of the pharmaceutical industry in Korea through both direct and indirect channels, examining the influence of the PLS on sales profit and cash flow.

Methods

Data from 9 years (5 before and 4 after PLS implementation) were drawn from the financial statements of firms whose stocks were exchanged in 2 official stock markets in Korea (526 firms) and additional pharmaceutical firms whose financial performance was officially audited by external reviewers (263 firms). Longitudinal analyses were conducted, using the panel nature of the data to control for permanent unobserved firm heterogeneity.

Results

Our results showed that the PLS was directly associated with R&D investments. In contrast, its indirect impacts stemming from the influence on sales profit and cash flow were minimal and statistically nonsignificant. The gross impact of the PLS on R&D investments increased moving further from the enactment year; R&D investments were reduced by 18.3% to 25.8% in 2009–2010 (compared with before PLS implementation) in the firm fixed-effects model. We also found that such negative direct and gross impacts of the PLS on R&D investments were significant only in firms without newly developed chemical entities.

Conclusion

Considering the gross negative impact of the PLS on R&D investments of pharmaceutical firms and the heterogeneous response of these firms by the R&D activities, governmental efforts of cost-containment may need to consider the spillover impact of the PLS on pharmaceutical innovation.     

临床药师参与1例胃癌术后腹腔感染合并蜂窝组织炎患者的药学监护

目的 通过临床药师参与1例胃癌术后腹腔感染合并蜂窝组织炎患者的治疗,探讨术后感染治疗的药物选择及药学监护与对患者的用药教育。方法 临床药师从药学角度结合临床实际去思考患者的药物选择,在治疗过程中,与医师沟通、协助医师优化治疗方案,对患者进行用药教育等方式,参与患者的药学监护过程。结果 在临床药师的干预下,医师更改用药方案,在一定程度上促使患者感染症状得到有效控制,病情逐渐好转至出院。结论 临床药师结合专业知识选择最优的抗菌药物方案治疗术后感染,给予患者全方位药学监护,体现了药师在药学监护中的重要性。     

噻吗心安和溴莫尼定滴眼液对兔眼表组织的影响

目的 探讨降眼压药物噻吗心安滴眼液和溴莫尼定滴眼液及各自的防腐剂硫柳汞和氯化笨甲烃胺(BAC)对兔眼表组织的影响.方法 15只新西兰大白兔,随机分为对照组(3只)、噻吗心安组(T组,6只)和溴莫尼定组(B组,6只).实验兔右眼使用噻吗心安或溴莫尼定滴眼液,左眼使用对应的防腐剂硫柳求和BAC,每日2次,连续用药30 d.取球结膜组织进行HE染色并计数结膜上皮层炎性细胞数;角膜行扫描电镜检测并进行上皮损害分级评分.结果 HE染色示对照组兔球结膜上皮细胞排列整齐,用药后各组结膜上皮细胞层数增多,排列较对照组紊乱.与对照组比较,噻吗心安滴眼液、溴莫尼定滴眼液、防腐剂硫柳汞和BAC均可导致球结膜上皮层炎性细胞浸润增多(55.8+6.9,71.0±8.8,56.0±7.1,62.5±7.1比32.3±8.8,均P<0.05).角膜扫描电镜示除对照组外其他各组角膜上皮细胞表面的微绒毛丢失、细胞空洞和暗细胞增加;各实验组角膜上皮损害评分均高于对照组(P<0.05).溴莫尼定滴眼液引起的损害较噻吗心安滴眼液明显(P<0.05),但两种滴眼液和对应的防腐剂对左右两眼的损害差异无统计学意义(P>0.05).结论 噻吗心安、溴莫尼定滴眼液及防腐剂硫柳汞和BAC使用1个月后可导致兔球结膜炎性细胞增加和角膜上皮细胞损伤;防腐剂是引起眼表损伤的主要原因.溴莫尼定滴眼液对兔眼表的损伤较噻吗心安滴眼液严重.     

采用细胞毒性试验对23个药用包装材料进行生物安全性评价

目的：用体外细胞毒性试验对23个药用包装材料进行生物安全性评价,探讨样品浸提液制备方法对检测结果的影响。方法：设定样品质量/浸提液体积比值为0.2 g/mL,药用包装材料分别用MEM培养基(37℃、24 h)、氯化钠注射液和去离子水(121℃、1 h)制备浸提液。小鼠成纤维细胞L929培养于96孔板中,每孔加入样品浸提液100μL培养48 h后,用酶标仪测定吸光度值,根据细胞的相对增殖度(RGR)进行细胞毒性反应分级,≤1级为阴性,2级为可疑阳性,≥3级为阳性。结果：23个受试样品的MEM培养基浸提液均为0～1级;氯化钠注射液浸提液检出9个受试样品为2级以上,其中3个为3级以上;用去离子水浸提液复核9个受试样品可疑阳性结果,仅3个为2级以上,其中1个为3级。结论：体外试验在排除渗透压、pH值等的干扰,用最大溶出度浸提液作为溶剂配制培养基进行试验,能够明显增加药用包装材料毒性反应阳性结果的检出率。     

药物分析中固相萃取法微课的开发与教学实践

文章从药学专业人才培养角度出发,设计、制作与应用药物分析微课教学.以体内药物分析中固相萃取法为例,在对其教学目标和教学重点、难点分析的基础上,进行微课教学设计,将微课主要的环节分为复习和导入、讲授教学内容、小结与拓展几部分,突出任务驱动和启发式教学,通过知识可视化增加微课的生动性;然后在微课脚本基础上,完成微课拍摄和制...