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

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

同志社女子大学における薬学部と看護学部の協働でのInterprofessional Education の取り組み

In the spring semester of 2021, the Faculty of Pharmaceutical Sciences and the Faculty of Nursing of Doshisha Women’s College of Liberal Arts jointly conducted wheelchair experience training for the 1st-year students as a multidisciplinary education. We conducted a questionnaire survey on pharmacy and Nursing students before and after training in order to assess the effect of interprofessional education and analyzed the report after the training using text mining method. Questionnaire items are the importance of each item related to interprofessional collaboration, KiSS-18 (Kikuchi’s scale of social skills: 18 items), RIPLS (readiness for interprofessional learning scale). The students of both faculties evaluated themselves quite high for even before the training and retained after the training. However, they may misunderstand or understand not quite well about their professional roles and mutual cooperation in the real clinical settings. It was found that it is necessary to further enhance the prior education on the knowledge content about IPE論