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138 巻, 9 号
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受賞総説
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赤池 昭紀2018 年 138 巻 9 号 p. 1127-1133
発行日: 2018/09/01
公開日: 2018/09/01
ジャーナル フリーI joined efforts to promote the pharmaceutical education system by participating in committees for developing a model core curriculum for pharmaceutical sciences (core curriculum), in pharmacist educator workshops, in the development of a pharmaceutical common achievement test, evaluation of pharmaceutical education programs, and the creation of a national examination for pharmacists. This review outlines the efforts to reform these pharmaceutical education systems. The core curriculum was prepared under the initiative of the Pharmaceutical Society of Japan. Pharmacist educator workshops were frequently held for the training of educators engaged in the six-year undergraduate course. The Subcommittee of Pharmaceutical Sciences of the Science Council of Japan also held workshops for the development of pharmaceutical education. Under these efforts, the education system consisted of the six- and four-year courses started in 2006. The Ministry of Health, Labour and Welfare revised the national examination for pharmacists. More than 10 years after formulating the core curriculum, the Ministry of Education, Culture, Sports, Science and Technology led the reform of the core curriculum in 2013. The basic idea of the revised core curriculum is outcome-based education. Minor revisions to the national examination for pharmacists were also made following this revision of the core curriculum. The Subcommittee of Pharmaceutical Sciences of the Science Council of Japan conducted reference standards for pharmaceutical sciences to promote education and research in the four-year course. Thus, we created education systems for developing pharmacists and researchers capable of contributing to medical care through the creation, production, and proper use of medicines.
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大岡 伸通2018 年 138 巻 9 号 p. 1135-1143
発行日: 2018/09/01
公開日: 2018/09/01
ジャーナル フリーProtein knockdown technologies based on small molecules are attracting considerable attention in the pharmaceutical industry as a strategy for novel drug discovery. We and others have developed such compounds, designated as Specific and Nongenetic Inhibitor of Apoptosis Protein (IAP)-dependent Protein Erasers (SNIPERs), proteolysis-targeting chimeras (PROTACs), and Degronimids, which induce selective degradation of target proteins. These compounds contain two different ligands, specific for an ubiquitin E3 ligase and for a target protein, respectively, connected by a linker. SNIPERs, PROTACs, and Degronimids are designed to cross-link E3 ligase and the target protein to induce polyubiquitylation and proteasomal degradation of the target protein within cells. To recruit the von Hippel-Lindau (VHL) E3 ligase complex and the cereblon (CRBN) E3 ligase complex, a VHL inhibitor and a thalidomide derivative have been integrated into PROTAC and Degronimid constructs, respectively. Similarly, an IAP antagonist has been incorporated into SNIPERs to recruit cellular inhibitor of apoptosis protein 1 (cIAP1) or X-linked inhibitor of apoptosis protein (XIAP) E3 ligase. To date, a range of such compounds have been developed, allowing selective degradation of a variety of proteins, including estrogen receptor α (ERα), oncogenic kinase BCR-ABL, and epigenetic regulator bromodomain-containing protein 4 (BRD4). Some compounds have also demonstrated ability to degrade target proteins in vivo, suggesting that this technology is feasible for use in novel drug development.
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土岐 浩介2018 年 138 巻 9 号 p. 1145-1150
発行日: 2018/09/01
公開日: 2018/09/01
ジャーナル フリーAntiarrhythmic drugs require therapeutic drug monitoring (TDM) to avoid adverse effects such as proarrhythmia. However, TDM is not necessarily used to adjust the dosage of antiarrhythmic drugs because there is a lack of information regarding the therapeutic range of the serum concentration and the selection of patients who require TDM. The aim of this review was to provide an overview of the pharmacogenetic information on the pharmacokinetics and drug response of flecainide, a class Ic antiarrhythmic drug with a sodium channel-blocking effect. A population pharmacokinetic analysis revealed that the CYP2D6 genotype was a determining factor of the age-related decline in flecainide clearance. Elderly patients show large interindividual variability of flecainide clearance because they have a more pronounced effect of the CYP2D6 genotype and require more frequent monitoring of serum flecainide concentrations. Carriers of an Asian-specific promoter haplotype B of the cardiac sodium channel gene (SCN5A) more frequently achieve clinically relevant flecainide efficacy even at lower concentrations. This suggests that the therapeutic range of serum flecainide concentrations is lower in SCN5A promoter haplotype B carriers than in the wild-type haplotype A homozygotes. The β1-adrenergic receptor Gly389 polymorphism decreases the antiarrhythmic efficacy of flecainide when co-administered with β-blockers. Carriers of Gly389 with co-administration of β-blockers may not achieve clinically relevant flecainide efficacy even when the serum flecainide concentrations are within the therapeutic range. These findings provide pharmacogenetic information for the effective utilization of TDM in antiarrhythmic drug therapy.
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杉本 健士2018 年 138 巻 9 号 p. 1151-1161
発行日: 2018/09/01
公開日: 2018/09/01
ジャーナル フリーNitrogen heterocycles are important skeletons in biologically active compounds such as medicines and natural alkaloids. However, in terms of the efficiency of the synthetic process, the many synthetic steps required to achieve the target compounds with complex architectures pose a significant problem. To overcome this challenge, novel approaches were developed to afford biologically active heterocycles, 1,2-diazepines, pyrroloisoquinolines, and pyrrolizidines utilizing cascade reactions that enable multiple bond formation in a one-pot process. This review discusses three one-pot reactions: 1) 1,2-diazepine synthesis from cyclobutenones and lithiodiazoesters via cascade 4π-8π electrocyclization; 2) synthesis of pyrroloisoquinolines from alkynylimino esters triggered by gold-catalyzed azomethine ylide formation; and 3) pyrrolizidine synthesis via three-component coupling reactions of iminoesters, acetylenes, and maleimides through the gold-catalyzed azomethine ylide generation/[3+2]-cycloaddition/enamine cyclization reaction.
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門田 和紀2018 年 138 巻 9 号 p. 1163-1167
発行日: 2018/09/01
公開日: 2018/09/01
ジャーナル フリーFor efficient and deeper drug delivery into the lungs via dry powder inhalers (DPIs), we designed porous spray-dried particles (SDPs) containing anti-tuberculosis drugs and sugar-based excipients. The SDPs were prepared by spray-drying ethanol solutions containing isoniazid and/or rifampicin and sucrose, maltose, or highly branched cyclic dextrin (HBCD). Solid-state fluorescence emission spectroscopy showed that 1-naphthoic acid (1-NPA), a model drug, was dispersed in a molecular dispersion/solid solution, suggesting high potential of HBCD as an excipient in DPIs. 1-NPA was dispersed not only as active pharmaceutical ingredient (API) molecules with HBCD, but also as fine crystals. Morphological examination showed that the fine particles of HBCD/anti-tuberculosis drugs were porous, indicating high aerodynamic performance. Isoniazid and rifampicin could also be incorporated into the HBCD matrix. HBCD formulations exhibited higher released doses and fine-particle fractions than sucrose and maltose formulations, and could incorporate both hydrophilic and hydrophobic drugs.
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一般論文
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村田 勇, 西山 大青, 川崎 浩範, 内藤 千鶴, 鎌田 武志, 古河 義行, 岩田 萌子, 杉野 雅浩, 井上 裕, 金本 郁男2018 年 138 巻 9 号 p. 1169-1179
発行日: 2018/09/01
公開日: 2018/09/01
ジャーナル フリー
電子付録In patients with cancer, it is difficult to continue medical treatment owing to nausea and vomiting (NV). Therefore, it is important to avoid these problems for improving the patient's QOL. Rikkunshito extract (RK) possesses antiemetic effects and is used in combination in cancer therapy. However, patients with cancer find it difficult to take the medicine orally for the treatment of NV and anorexia owing to the characteristic smell and taste of traditional Chinese medicine. We examined the pharmaceutical properties of RK suppository for hospital use, assessed bioequivalence by using pharmacokinetic parameters, and determined its effectiveness against NV and anorexia in rats. In this study, RK suppository was prepared by using RK formulation (A, B, and C) and Witepsol (H and S) (AH, BH, CH, AS, BS, and CS). Pharmaceutical properties, namely, hardness, dispersibility, long-term stability, and drug (hesperidin and glycyrrhizic acid) release were measured for AH, BH, AH, and AS. The pharmacokinetic parameters, effectiveness of substance P against NV and anorexia, and serotonin-activated ghrelin levels were assessed for BH only. AH, BH, AS, and AS demonstrated uniform and sufficient hardness. The release rate of oleaginous components, such as glycyrrhizic acid, did not change significantly, while that of water soluble components, such as hesperidin, decreased when compared with that in powder formulations A and B. NV and anorexia improved in rats administered BH compared with the control group. BH suppository showed effectiveness in terms of both physicochemical property and bioequivalence for hospital use.
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鏡 圭介, 今井 俊吾, 田澤 佑基, 岩崎 澄央, 福元 達也, 秋沢 宏次, 山田 武宏, 石黒 信久, 井関 健2018 年 138 巻 9 号 p. 1181-1189
発行日: 2018/09/01
公開日: 2018/09/01
ジャーナル フリーOnly minimal information exists regarding the treatment outcomes of patients suffering from methicillin-resistant Staphylococcus aureus (MRSA) bacteremia treated with teicoplanin (TEIC) when the TEIC minimum inhibitory concentration (MIC) is close to the upper limit of the “susceptibility range” according to the Clinical Laboratory Standards Institute (CLSI). We investigated the outcome of TEIC-treated patients in MRSA bacteremia, focusing on TEIC MIC against MRSA. A retrospective cohort study was conducted on patients with MRSA bacteremia. TEIC treatment failure was defined as any of the following: (1) all-cause 60-day mortality, (2) persistent bacteremia until the end of TEIC treatment, or (3) 30-day recurrence of MRSA bacteremia. Nineteen patients were enrolled, of whom 15 exhibited TEIC MICs ≤2 μg/mL and the remaining 4 exhibited >2 μg/mL. The rate of treatment failure and all-cause 60-day mortality in patients with MIC >2 μg/mL were significantly higher than those in patients with MIC ≤2 μg/mL [4 patients (100%) versus 4 patients (26.7%) (p=0.018) and 4 patients (100%) versus 2 patients (13.3%) (p=0.004), respectively]. Three of four patients (75%) with MIC >2 μg/mL had persistent bacteremia, which was quantitatively higher than in patients with MIC ≤2 μg/mL (1 of 7 patients, 14.3%). Our finding suggests that TEIC MIC >2 μg/mL may be related to poor treatment outcome in MRSA bacteremia, and that TEIC should not be used in this case.
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山本 昌弘, 土屋 直, 飯島 志行, 竹内 洋文, 神谷 秀博2018 年 138 巻 9 号 p. 1191-1199
発行日: 2018/09/01
公開日: 2018/09/01
ジャーナル フリーIn order to characterize the adhesion and deformation behavior between chitosan-modified liposomes and the mucin layer of the small intestine, mucin was coated on hydrophobic surface-modified carbon nanotube (CNT) probe of an atomic force microscope. The interaction between this mucin layer and the liposomes with or without chitosan modification in phosphoric acid buffer solution was determined by atomic force microscopy. The pH of the buffer solution was controlled at 2.8 and 7.0. The chitosan modification increased the attractive force between the liposomes and mucin layer during the separation process under both pH conditions. This result corresponded with that from a previous study about the liposome adhesion behavior on the surface of the small intestine of rats. By using the mucin-coated CNT probe, the long range and different types of attractive forces between the chitosan-modified liposomes and mucin layer was observed. Furthermore, the small-scaled deformation behavior change on the liposomal surfaces due to chitosan modification was also observed by the CNT probe. The detail deformation and adhesion behavior of the liposomes with or without chitosan modification was detected.
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小野 秀樹, 岡村 真彩, 福島 章紘2018 年 138 巻 9 号 p. 1201-1215
発行日: 2018/09/01
公開日: 2018/09/01
[早期公開] 公開日: 2018/06/20ジャーナル フリーThe anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as “clinically significant adverse reactions”, and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.
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橋本 良太, 藤井 景子, 吉田 和子, 下路 静佳, 正木 秀典, 角山 香織, 中村 敏明, 恩田 光子2018 年 138 巻 9 号 p. 1217-1225
発行日: 2018/09/01
公開日: 2018/09/01
ジャーナル フリーThe current study aimed to examine the outcomes of pharmacists' involvement with elderly people in special nursing homes. We analyzed 58 cases involving regular visits by community pharmacists to 41 residents. The residents' mean age was 87.8±6.9 years, and 68.3% were prescribed 6 or more types of medication. Antipsychotic and insomnia medication was taken by 24.4% and 31.8% of residents, respectively. Pharmaceutical consultation following medication use accounted for 60.3% of pharmacists' involvement with residents. The outcomes of these consultations included improvements in prescription content; the identification and prevention of adverse drug events; improvement in activities of daily living; and improvement in test results, sleep, and urination/bowel control. The results also suggested that pharmacists' intervention reduced drug costs. Information that facilitated involvement was most frequently acquired via conversations (67.2%) and conferences (24.1%) in the facilities. The most common information sources were care workers (72.4%), followed by nurses (37.9%), physicians (6.9%), and functional training instructors (6.9%). Information was also acquired from patients (3.4%) and their family members (5.2%). The findings indicated that regular visits by pharmacists to facilities for elderly people and conversations between residents, their family members, and physicians, nurses and various other professionals improved various pharmacotherapy outcomes.
抄録全体を表示Editor's pickThe current study aimed to examine the outcomes of pharmacists’ involvement in special nursing homes. We analyzed 58 cases involving regular visits by community pharmacists. Pharmaceutical consultation following medication use accounted for 60.3% of pharmacists’ involvement with residents. The outcomes of these consultations included improvements in prescription content; the identification and prevention of adverse drug events; improvement in ADL. The findings indicated that regular visits by pharmacists to facilities for elderly people and communicate with care professionals improved pharmacotherapy outcomes.
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