The Influence of the Shape of the Plasma Drug Concentration Profile upon the Pharmacological Effect

Pharmaceutical Research -     

UPLC-MS/MS测定大鼠舌下静脉注射阿西替尼的血药浓度及其药动学研究

目的 建立UPLC-MS/MS对舌下静脉注射大鼠血浆中阿西替血药浓度的检测方法,并进行其药动学研究。方法 乙腈沉淀法处理样品,以伊马替尼为内标,Waters Acquity BEH C₁₈色谱柱（2.1 mm×100 mm,1.7 μm）,流动相为0.1%甲酸水和乙腈。流速为0.3 mL·min^-1,柱温35℃。质谱条件为电喷雾电离源（ESI）,检测方式为正离子电离、多离子反应监测（MRM）检测。结果 阿西替尼血药浓度在0.1~100 ng·mL^-1内线性关系良好（r=0.999 6）,定量下限为0.1 ng·mL^-1。日内、日间精密度RSD<5.56%,提取回收率>87.87%。大鼠血浆中的阿西替尼在室温、4℃,-80℃,12 h后以及反复冻融3次后均有良好的稳定性,且不存在基质效应。结论 建立的测定阿西替尼血药浓度的方法准确、简单、快速,可以为阿西替尼的临床研究提供实验参考和依据。     

A New Route of Drug Administration: Intrauterine Delivery of Insulin and Calcitonin

High molecular weight drugs in general, and peptides in particular, are usually delivered by parenteral route because they are poorly absorbed or degraded in the gastrointestinal tract. To optimize therapy, it is desirable to search for nonparenteral routes of administration and to deliver the drug in a controlled-release fashion. We report here on the absorption and the systemic biological effect of two peptides, insulin and calcitonin, after instillation into the uterus of the rat. Intrauterine delivery was compared to subcutaneous injections in intact and ovariectomized rats. In addition, we describe results of a preliminary study on calcitonin absorption from controlled-release matrices inserted in the rat uterus. The amount and duration of the hypoglycemic and the hypocalcemic effects induced by intrauterine delivery of insulin and calcitonin, respectively, were equivalent to those obtained after subcutaneous injections. The results were similar in intact and ovariectomized rats. It is concluded that the intrauterine administration of both insulin and calcitonin is bioequivalent to subcutaneous injection. The therapy of a number of clinically important diseases could benefit from this discovery.     

Discrepancies between predicted and observed rates of intravenous gentamicin delivery for neonates

Objectives This study aimed to investigate intravenous infusions as used in the neonatal intensive care setting, to determine the effect of gentamicin dose (mg), gentamicin concentrations (mg/ml), flow rate (ml/h) and flush volume (ml) upon the length of infusion time. Methods Intravenous infusions were set up to simulate administration of gentamicin to neonates. Dextrose (10%, w/v) was administered as the primary intravenous fluid at 3.8 or 18.7 ml/h. Gentamicin doses (0.5 mg/0.2 ml, 2 mg/0.2 ml, 2.5 mg/1.0 ml, or 10 mg/1.0 ml) were delivered into the intravenous line at a T‐connection using a Graseby pump over 35 min. This was followed by a saline flush of 1 or 2 ml over a further 35 min. At the end of each experiment a 2 ml 0.9% saline bolus was given. Analysis of gentamicin collected at 5‐min intervals was by an HPLC method. Key findings The experiment demonstrated that under the infusion conditions neonates weighing 2.5 kg would receive only 80% of the drug at 60 min, increasing to 90–95% by 75 min. In extremely low birth weight neonates (0.5 kg), even lower percentage of gentamicin recovery occurred. At 60 min only 60% of the intended gentamicin dose had been delivered and this increased to only 70% by 75 min. Conclusions The delivery of gentamicin administered by intravenous infusion is substantially extended in extremely low birth weight neonates. This appeared to be primarily due to the small volumes and low infusion rates used in these patients.     

Pharmacokinetics of Droperidol in Healthy Volunteers Following Intravenous Infusion and Rectal Administration from an Osmotic Drug Delivery Module

Pharmaceutical Research -     

静滴大剂量氨甲蝶呤／醛氢叶酸治疗血液肿瘤的血药浓度及药效学

目的：本文对不同时间静滴大剂量氨甲蝶呤／醛氢叶酸解救治疗血液肿瘤患者的血药浓度进行监测及药效和毒性反应进行研究。方法：采用高效液相色谱法测定氨甲蝶呤的血药浓度,按不同时间静滴大剂量氨甲蝶呤将４１例病人分为两组;Ｓ组氨甲蝶呤于６ｈ滴完,Ｌ组于１２ｈ滴完,两组均在滴注完６ｈ开始醛氢叶酸救援。在滴注毕０．８、６、４２ｈ采血测定氨甲蝶呤血药浓度。结果：Ｓ组药物浓度在０．０８ｈ显著高于Ｌ组（Ｐ＜０．０１）,６、１８、４２ｈ两组血药浓度无差异（Ｐ＞０．０１）。完全缓解率中位持续完全缓解及中位生存期两组间无显著差异（Ｐ＞０．０５）,Ｌ组毒性反应明显比Ｓ组严重。结论：６ｈ滴完组的疗效比１２ｈ滴完组的好。     

对我州食品药品监管体制改革的思考

目的探讨基层食品药品监管体制改革模式与方案,为全州食品药品安全监管体制改革提供科学依据。方法采用召开座谈会、发放调查问卷、实地走访企业等调研方法 ,分析全州餐饮消费环节食品安全、保健食品、化妆品监管现状。结果建立权威高效的食品药品监管体制、科学设置食品药品监管机构、整合优化食品药品监管队伍,是推进我州食品药品监管体制改革的重要举措。结论构建统一、独立、高效的食品药品安全监管体制,强化食品药品监管,提高监管效能,是保障公众饮食用药安全的需要。     

论我国药品监督管理体制的特征及实践问题

本文对药品监督管理体制的本质特征，执法主体，省，市药品监管机关在垂直体制法律关系中的地位变化作了分析。并提出需要在实践中认真思考和回答的问题。     

吡罗昔康口服和局部给药后药物动力学和局部组织的分布

目的 研究大鼠吡罗昔康局部给药的药物传递和机理。方法 大鼠分别局部给药和口服4mg吡罗昔康后，用HPLC法测定局部给药部位的皮肤、肌肉、关节和血液的药物浓度。结果 口服给药后，Tjoint/Plasma和Tmus/Plasma比值保持恒定，大部分的时间其值介于0．06和0．2。比较而言，局部给药后，Tjoint/Plasma和Tmus/Plasma比值分别介于0．2到1．26和1．89到5．4之间。比值远远大于口服给药。结论 数据表明局部给药后，到达局部深层组织的吡罗昔康来自于药物的直接渗透；当药物的靶向部位在局部时局部给药优于口服给药。     

美国FDA哨点行动及其对我国食品药品监管数据管理的启示

目的：介绍美国FDA哨点行动背景、项目、内容、特点,为我国食品药品监管数据共享利用和管理提供参考。方法：使用文献研究的方法,围绕美国食品药品管理局哨点行动计划收集材料并梳理分析。结果与结论：信息化和大数据时代背景下数据资源共享与食品药品监管业务工作密不可分;顶层支持有助于数据协同共享等工作开展;分布式数据管理模式值得借鉴;产学研结合有助于开展数据分析挖掘;相关方广泛参与有助于从源头保障数据质量。     

1012例住院患者静脉注射剂使用情况调查分析

目的了解静脉注射剂在临床使用过程中的药物不良反应（ADR）及其特点,以促进合理用药。方法调查1012份出院病历用药医嘱,对使用静脉注射剂发生的ADR进行回顾性分析。结果使用中药注射剂的ADR发生率较高。联合用药会增加ADR的发生率。结论应按照推荐的常规使用方法和疗程使用静脉注射剂,并注意药物联用时可能引起的不良反应。     

司替戊醇及其自纳米乳在大鼠血浆和脑组织中的药物浓度比较

目的:建立测定大鼠血浆和脑组织中司替戊醇(STP)质量浓度的方法,并比较STP及其自纳米乳在血浆、脑组织中的药物浓度.方法:以占吨酮为内标,采用高效液相色谱-荧光检测法(HPLC-FLR)测定.色谱柱为Diamonsil C18,流动相为乙腈-25 mmol/L KH2PO4水溶液[44:56(V/V),pH 2.6]...     

对基层食品药品监督机构行政执法案卷的调查分析

目的了解基层食品药品监督机构的执法状况,探讨其行政处罚的特点与规律。方法对19个基层食品药品监督管理机构成立7年来全部行政处罚案卷进行调研并分析。结果基层药械执法工作虽取得显著成效,但仍存在诸多不尽人意之处。结论基层药械执法工作者务必增强依法行政的意识,不断提升药械执法的效率与质量。     

Assessment of Patient Exposure to Leachables From Lyophilized Drug Formulations Following Reconstitution,Storage, and Administration via Polymeric Packaging/Delivery Systems

It has been demonstrated that lyophilized drug formulations have an increased propensity to leach substances from the rubber stoppers comprising their primary packaging system when compared to aqueous liquid formulations stored in the same manner. Unfortunately, patient exposure to leachables originating in lyophilized drug products is not known. To that end, the goal of this study was to assess patient exposure to these leachables after reconstitution, storage, and administration of the lyophilized drug. To achieve this goal, several leachables present in 2 commercial lyophilized drug products were quantified after contact with polyvinyl chloride and non–polyvinyl chloride medication bags as well as an infusion set for durations of 15 min to 7 days at refrigerated and ambient temperature. The results obtained from this study showed that the bag’s material of construction and the drugs formulation did not impact the mass of the leachables administered. Conversely, the mass of each leachable administered to the patient was reduced or eliminated as the contact duration with the intravenous bag and the temperature increased. However, for shorter contact durations, refrigerated storage, and higher molecular weight compounds, the patient would be exposed to a majority of the leachables originating from the vial.     

Contribution of Intravenous Administration Components to Subvisible and Submicron Particles Present in Administered Drug Product

Particulate matter present in drug products intended for parenteral administration to patients is typically monitored and controlled in the finished drug product to minimize potential risks to patients. In contrast to particulates found in drug products, the current study evaluated particulates representative of materials and operations typically used in the dose preparation and administration of drug products. A comprehensive assessment of intrinsic and extrinsic sources of subvisible and submicron particulates arising from materials associated with subcutaneous and intravenous dose preparation and administration was conducted. In particular, particles arising from disposable syringes, commercial sterile diluents, and intravenous supplies were quantitated using established methods for subvisible (light obscuration, flow imaging) and submicron particles (resistive pulse sensing). Each of these sources contributed varying amounts of particulates; therefore, owing to sources from materials required for administration, it is inadequate to assume that the total particulate load delivered to patients arises solely from the drug product. Careful consideration of the administration method and supplies used can improve the predictability of particulate levels present in dose preparations or administration volumes.