Gemfibrozil absorption and elimination in kidney and liver disease

Summary The disposition of the lipid-lowering drug gemfibrozil was studied in patients with either renal (n= 8) or hepatic disease (n= 8) and compared to those of healthy volunteers (n= 6). Gemfibrozil was determined in plasma and urine by means of a HPLC method. Urine was also analyzed for gemfibrozil conjugates.Following oral administration of 900 mg gemfibrozil, maximal plasma levels of the parent drug were 46.1±15.8 g/ml, attained after 2.2±1.1 h. In chronic renal failure and in liver cirrhosis the plasma concentrations of gemfibrozil did not significantly differ from that of controls except in those patients who were comedicated with antacids. These patients had significantly lower C_max and AUC values. The elimination half-life of the drug was 1.5 h in controls, 2.4 h in renal failure, and 2.1 h in liver disease. In healthy volunteers, only 0.02 to 0.15% of the given dose was recovered in the urine as parent gemfibrozil, while conjugates made up 7–14%. In patients with renal failure also, only traces of parent gemfibrozil could be detected, and conjugates accounted for 0.5–9.8%. In those with liver disease, however, about 0.1–0.2% were recovered in urine as parent gemfibrozil and up to 50% as conjugates. Strikingly, the amount of excreted conjugates in the urine was positively correlated to the direct bilirubin plasma concentration. It can be concluded that the elimination of gemfibrozil is not significantly influenced by renal failure. However, comedication with antacids markedly reduced plasma disposition of the drug. Patients with severe liver disease excreted more conjugated gemfibrozil via the kidney than did healthy controls. Thus, transfer across the canalicular cell membrane to the bile duct, rather than drug metabolization, is primarily disturbed in liver disease. Gemfibrozil accumulation is unlikely to occur in either kidney or liver disease.Abbreviations Cl_r creatinine clearance (ml/min) - HPLC high pressure liquid chromatography - C_max maximal plasma concentration (g/ml) - t_max time (h) after which C_max is attained - k_e elimination rate constant (h^–1) - t_1/2 elimination half-life (h) - A_e amount of drug excreted into the urine (% of given dose) - MRT mean residence time (h) - AUMC area under the first moment curve (g h²/ml) - AUC area under the plasma level time curve (g·h/ml) - ANOVA analysis of variance The paper is gratefully dedicated to G.W. Löhr     

无锡市控制和消灭脊髓灰质炎现状

目的 通过对无锡市控制与消灭脊髓灰质炎（下称脊灰）的现状分析，提出要继续保持高水平的急性驰缓性麻痹（AFP）病例监测系统敏感性，特别要作好流动儿童常规免疫和强化免疫工作，及时发现、应对各种野病毒输入情况，才能巩固无脊灰成果。方法 根据对该市人群免疫水平、疫苗免疫原性监测及15岁以下儿童的（AFP）病例监测系统的敏感性评价等分析该市控制与消灭脊灰的现状。结果 控制与消灭脊灰的现状分析结果表明，人群有较好的免疫水平，AFP监测系统敏感；但是，免疫空白的外来儿童是控制和消灭脊灰的薄弱环节，应引起高度重视。结论 该市的控制和消灭脊灰的现状表明，从上世纪印年代使用脊灰疫苗（OPV），特别是实施儿童计划免疫以来，接种率和人群免疫状况维持和稳定在较高水平。上世纪90年代脊灰发病已得到有效控制，已连续15a无脊灰野毒病例报告。要继续保持高水平的AFP病例监测系统敏感性，特别要作好流动儿童常规免疫和强化免疫工作，及时发现和应对野病毒的输入，才能巩固无脊灰成果。     

科技引领 技术创新|为加速消除疟疾进程提供驱动力

江苏省启动消除疟疾行动以来，在疟疾流行病学、病原生物学和媒介生物学等方面开展了系列科学研究，并建立了一些新技术和新方法，这不仅为江苏省消除疟疾提供了有力保障、有效阻断了本地疟疾传播，还为全国乃至全球消除疟疾提供借鉴和技术支持。     

Status of vaccine research and development of vaccines for malaria

Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding.     

输入性疟疾再传播风险评估指标体系的构建

目的　构建输入性疟疾再传播风险评估指标体系。方法　通过文献综述、专题讨论初步构建输入性疟疾再传播风险评估指标体系。选择26名疟疾防治专家,采用德尔菲法对指标体系开展2轮专家咨询,根据专家对每项指标的熟悉程度、判断依据和重要性评价计算专家积极系数、专家权威系数、专家协调系数、各指标变异系数,根据上述结果进行指标筛选并计算各指标权重;采用Cronbach’s α系数评价指标体系信度,采用专家权威程度系数评价指标体系的内容效度,采用KMO检验和因子分析评价指标体系的结构效度。结果　共23名专家完成2轮专家咨询,最终构建了一个包含3个一级指标、7个二级指标、21个三级指标的输入性疟疾再传播风险评估指标体系。第2轮专家积极系数（100.00% vs. 88.46%）和专家协调系数（0.372 vs. 0.286, P均< 0.01）均高于第1轮。第2轮专家咨询后,各级指标专家权威程度系数为0.757～0.930,一、二、三级指标变异系数分别为0.098～0.136、0.112～0.276、0.139～0.335;指标体系整体Cronbach’s α系数为0.941;一（KMO值= 0.523,[χ2] = 18.192,P < 0.05）、二（KMO值= 0.694,[χ2] = 51.499,P < 0.01）、三级指标（KMO值= 0.519,[χ2] = 477.638,P < 0.01）KMO值均有统计学意义;三级指标6个主成分累积贡献率为84.23%。传染源、传播条件及防控能力3个一级指标归一化权重分别为0.337、0.333和0.329;归一化权重居前3位的二级指标依次为输入性病例数及虫种（0.160）、输入性病例入境及就诊情况（0.152）、媒介种类及密度（0.152）;归一化权重值居前5位的三级指标依次为输入性病例虫种（0.065）、媒介种群（0.064）、患者发病至就诊时间间隔（0.059）、输入性病例数（0.056）及从就诊至确诊时间间隔（0.055）。结论　成功构建了输入性疟疾再传播风险评估指标体系,为消除后开展输入性疟疾再传播风险评估和加强重点风险因素防控提供了科学依据。     

取不易守更难: 我国巩固消除疟疾成果面临的挑战

摘要］　2021年6月我国正式通过WHO消除疟疾认证,实现了消除疟疾目标。但目前全球疟疾流行形势依然严峻,近年来疟疾发病数和死亡数不降反升,我国传疟媒介仍将长期存在,巩固来之不易的消除疟疾成果任重道远。本文对我国当前疟疾防控工作中存在的困难与挑战进行分析,并提出下一步工作重点,旨在为防止疟疾输入再传播提供科学参考。     

监测与响应: 中国消除疟疾后的核心干预措施

2021年6月,我国顺利通过WHO消除疟疾认证。但我国每年仍有数千例境外输入疟疾病例,因输入性疟疾病例引起的死亡病例每年均有报告;由输入性疟疾导致的继发病例时有发生,由于原疟疾流行区传疟媒介依然存在,在疟疾消除地区由输入性病例再次引起本地传播的风险依然较大。本文就消除后阶段我国疟疾防控工作面临的风险、监测与响应工作中面临的挑战进行分析,并对今后工作重点提出相应建议。