Pharmacokinetic and pharmacodynamic evaluation of a new sustained-release capsules using starch-sponge matrix (SSM) release system for nifedipine in rats

We conducted a performance assessment study for a new sustained-release capsule including starch-sponge matrix (SSM). The SSM, which is a support medium for drug release, was made from 2.5% cornstarch glue by means of freezing dry method. The SSM capsule was applied for nifedipine (NFP), a calcium channel blocker, and evaluated pharmacokinetic and pharmacodynamic (PK/PD) profiles of NFP after intraduodenal administration of SSM capsules including 2.5 or 5.0 mg of NFP per capsule to rats. Plasma NFP concentrations from the SSM capsules showed dose-dependent increases with a Michaelis-Menten like behavior over 360 minutes after intraduodenal administration. The values of area under the concentration vs. time curve from time zero to 360 min (AUC0-360) of NFP declined in making SSM capsules as compared to control capsules due to a simple physical mixture of NFP and cornstarch, but the values of mean residence time (MRT0-360) extended and abidingness of SSM capsules were admitted with dose-dependent manner. As for a PD parameter, the mean arterial blood pressure (mABP) derived from the SSM capsules showed 15~20% decrease of baseline within 120min after intraduodenal administration, and thereafter the mABP in 2.5 mg SSM capsule was gradually recovered, while a relatively smooth and even change was found in the mABP at 5.0 mg SSM capsule. The relationships between plasma NFP concentration and sampling-time corresponding mABP after intraduodenal administration of SSM capsules showed no rapid change in the mABP, indicating that a sustained-release mechanism due to the SSM functions sufficiently to avoid a fluctuating blood pressure accompanied by going up and down of plasma levels of NFP. The SSM capsules exhibited a sustained-release pharmacokinetics of NFP, and made the fluctuation range with blood pressure small compared to the physical mixture preparations. Thus, it was evidenced that the SSM capsule is useful device to provide a sustained-release systems and optimal therapeutic efficacy of drugs.Keywords: Controlled-release, Cornstarch, Matrix, Nifedipine, Pharmacokinetics, Pharmacodynamics

先発医薬品・後発医薬品（錠剤）の溶出挙動の比較と評価

Dissolution test is mandatory to guarantee the quality of the generic pharmaceutical tablets, and generic pharmaceutical tablets must comply with this dissolution test to be approved. However, in this test, it is not clear what type of elution behavior to take, only byspecifying the dissolution rate at a fixed time. In this study, we aimed to clarify elution behavior of loxoprofen sodium 60 mg tablet (24 items) and nitrendipine 5 mg tablet (15 items) by measuring dissolution rate with time according to dissolution test of the JapanesePharmacopeia with some modification. Both drug showed good dissolution. The original brand loxoprofen tablets had comparatively small variation among tablets in elution behavior. For generic loxoprofen tablets, some of the dissolution rates were faster or slower. In some generic items, variations in elution behaviors were observed within the same item. In the original brand nitrendipine tablets, elution behavior showed slowly until 5 minutes, and then fast elution, and there was variation between the tablets by 15 minutes. Many of genericnitrendipine tablets showed variations in 5 to 15 minutes in elution behavior within the same item, but some showed little variations between tablets within the same item.論

同志社女子大学薬学部６年次生と看護学部４年次生に対する多職種連携教育の試み

超高齢化と医療の高度化・複雑化に伴い、チーム医療を行い、より医療の質を高め、効率的な医療サービスを提供することが求められている。チーム医療を推進するために多職種連携教育（IPE：Interprofessional Education）を学生の時期から行うことが必要であると提唱されている。そこで本学の実務実習を終えた薬学部６年次生と臨地実習を終えた看護学部４年次生を対象に、模擬的な臨床事例を共有し、シミュレーターを用いたフィジカルイグザミネーション、電子カルテからの情報を用いた演習、そしてグループワークを通して多職種連携に必要な能力を修得するためのIPE を試みた。授業終了後の学生のレポートから、学生は、自分の専門職としての役割や他の職種の役割を具体的に理解し、他職種と協働するには専門職間の相互理解と同時にコミュニケーション能力が重要であることを学修していた。今回のトライアルを受け、授業プログラムや教育方法を充実させ、段階的に授業効果を検証していくシステムを構築する必要があると考えられた。According to advent of super-aging society and the increasing sophistication and complexity of medical care, there is a need to provide team medical care to improve the quality of medical care and efficient medical services. In order to promote team medical care,it is advocated to provide interprofessional education from the time of students. By sharing simulated clinical case between sixth-year pharmacy students and fourth-year nursing students who have completed on-site practical training at this university, the interprofessional education was conducted, and where the students acquire the abilities required for multi-professional collaboration through physical examination using simulators, exercises using information from electronic medical records and/or group work. From the post-class student reports, it was considered that students learned that interprofessional communication as well as mutual understanding was important to understand specifically and cooperate in their professional and other roles in the clinical practice. Throughout this trial, we found that it is necessary to establish a system in which lesson programs and teaching methods are enhanced and the effects of lessons are verified step by step.論

High energy electron observation by Polar Patrol Balloon flight in Antarctica

We accomplished a balloon observation of the high-energy cosmic-ray electrons in 10-1000GeV to reveal the origin and the acceleration mechanism. The observation was carried out for 13 days at an average altitude of 35km by the Polar Patrol Balloon (PPB) around Antarctica in January 2004. The detector is an imaging calorimeter composed of scintillating-fiber belts and plastic scintillation counters sandwiched between lead plates. The geometrical factor is about 600cm^2sr, and the total thickness of lead absorber is 9 radiation lengths. The performance of the detector has been confirmed by a test flight at the Sanriku Balloon Center and by an accelerator beam test using the CERN-SPS (Super Proton Synchrotron at CERN). The new telemetry system using the Iridium satellite, the power system supplied by solar panels and the automatic flight level control operated successfully during the flight. We collected 5.7×10^3 events over 100GeV, and selected the electron candidates by a preliminary data analysis of the shower images. We report here an outline of both detector and observation, and the first result of the electron energy spectrum over 100GeV obtained by an electronic counter

先発後発医薬品の簡易懸濁法への適合性と操作性に関する評価

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ペプチド転移酵素Sortase A が触媒するtranspeptidation 反応に対するCa2＋濃度、反応温度、E105点変異、外因性金属イオンの効果に関する研究

Sortase A is a transpetidase from Staphylococcus aureus that recognizes five specific amino acid sequences, LPETG, and binds them to polyglycine on the cell wall surface, immobilizing the target protein on the cell wall surface. Sortase A contains one Ca2＋ as a co-factor in its structure, and Ca2＋ plays an important role in the enzymatic reaction. First, the time course of the enzymatic reaction, the optimal Ca2＋ concentration, and the optimal reaction temperature were investigated using wild-type Sortase A. Next, we focused on E105, an amino acid residue that has been reported to play an important role in Ca2＋ binding. We prepared point mutants in which E105 was replaced with non-coordinating Ala residues and coordinating amino acid residues (Asp, Cys, His) with Lewis base moieties on the side chains and examined the enzymatic reaction in the presence of Ca2＋ and its cognate elements, Mg2＋ and Sr2＋.The result was the clarification of the optimal Ca2＋ concentration and the optimal reaction temperature range for the enzymatic reaction. In the case of Ca2＋ in the wild-type and E105 mutants, the reactivity was WT ≈ E105D＜E105C＜E105A＜E105H, indicating that the enzymatic reaction is affected by the Lewis basicity of the ligand and the steric structure of the side chain. For Sr2＋, the same trend of reactivity as Ca2＋ was observed, but the overall reactivity decreased. However, for Mg2＋, reactivity was significantly decreased in all cases, indicating the significant effect of ionic radius on the enzymatic reaction.論