Vitamin K plays an important role in blood coagulation and bone formation. However, apart from the liver and bone, the role of vitamin K in other tissues remains unknown. Previously, we have reported on high concentrations of vitamin K in the mouse brain and investigated vitamin K conversion in brain tissue. This led us to hypothesised the possibility of vitamin K contributing significantly towards maintenance and function of the cranial nervous system. In this review, we summarise the synthesis of novel vitamin K derivatives, their neuronal differentiation inducing activities and the induction mechanism. The findings from this study will provide insights into the physiological roles of vitamin K in the brain.

Human serum albumin (HSA) and α1-acid glycoprotein (AGP) are the major drug-binding proteins in the blood and regulate the tissue transfer of bound drugs. We succeeded in clarifying the three-dimensional structure of AGP for the first time in the world from X-ray crystal structure analysis. Using a site-directed mutagenesis method by constructing yeast expression systems as well as the three-dimensional structure, we elucidated the properties of drug binding sites of AGP. We also found that structural change due to the interaction between AGP and cell membranes causes the release of bound drugs and reported an “AGP-mediated drug transport process.” Pancreatic cancer has an extremely low response rate to anticancer drugs compared to other cancers and is resistant to starvation of nutrients including fatty acids. We clarified that glutamine metabolism is involved in this tolerance. Furthermore, aiming at efficient drug delivery and effective treatment for pancreatic cancer, we focused on nitric oxide (NO) which increases pancreatic blood flow and has a cell-killing effect on tumors and surrounding stromal tissues. We successfully synthesized nitrated phenylbutyrate (NPB), which binds to HSA and has an antitumor effect in vitro and vivo. The binding of NPB to HSA is considered to be useful for delivery to tumors through the enhanced permeability and retention (EPR) effect and HSA receptors.

The School Education Law was revised in 2006, and the university pharmacy education system and the national pharmacist examination system were changed. In line with the advancement of medical technology and the division of labor, 16 years have passed since the length of undergraduate pharmacy education was extended from 4 to 6 years in order to foster highly qualified pharmacists. During this period, the curriculum for practical training has been revised, and lectures and exercises focused on clinical education have been incorporated to foster pharmacists who can be useful in the medical field. In the area of cancer drug therapy, the university provides students with opportunities to learn about the basic mechanisms of action and side effects of anticancer drugs, but there is little coverage of clinical guidelines and pharmacological management of the latest therapies, such as cancer immunotherapy. Prior to my arrival at Hoshi University, I was involved in clinical work and clinical research at an oncology hospital for 13 years. Since my arrival, I have been exploring the gap between oncology pharmacotherapy and pharmacy education, and have been working to fill it. We have incorporated new curricula, such as exercises in formulation suggestions, lectures to deepen understanding of guidelines and supportive care, and information on the latest cancer drug therapies, such as cancer immunotherapy. This paper outlines the pharmacy education required to produce pharmacists who can practice safe cancer drug therapy.

Important tasks performed by pharmacists include dispensing medicines based on prescriptions and explaining medication to patients. However, pharmacists are now required not only to perform these tasks but also to provide patients with pharmacotherapy that maximises the efficacy of drugs and minimises side effects. In particular, chemotherapy has a wide variety of side effects and a higher incidence of side effects than pharmacotherapy for lifestyle-related diseases. The Cancer Institute Hospital has conducted a oncology pharmacist outpatient clinic for patients undergoing chemotherapy, pharmacists meet with patients on an outpatient basis. The content of these visits includes assessing the severity of side effects and adherence to oral anti-cancer drugs, and proposing supportive therapy to doctors. This symposium will focus on hand–foot syndrome caused by 5-fluorouracil (5-Fu) anticancer drugs and molecular-targeted drugs, and will share information on skills in assessing the severity of these side effects and on side-effect management based on reducing doses of anticancer drugs, taking off drugs and proposing supportive therapy. Furthermore, how the pill counts and Self-report methods are used in clinical practice to assess adherence to oral anti-cancer drugs will be shared. Recently, trainees from insurance dispensing pharmacies have been accepted and training has been provided on the management of adverse effects of chemotherapy and adherence assessment of oral anticancer drugs in the oncology pharmacist outpatient clinic. This symposium will share details of pharmaceutical care practices such as side-effect management in chemotherapy and adherence assessment of oral anticancer drugs, and discuss the skills required for patient safety management.

Recent changes in the environment surrounding community pharmacists include “follow-up after dispensing” becoming mandatory, initiation of “certified pharmacy system with specific functions,” with the discussions on post-graduate training, lifelong training and specialization, refill of prescriptions, as well as pros and cons of hospital pharmacies in preparation for the 2022 dispensing fee revision. In this regard, since 2019, I have been receiving training at The Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR). In addition, to implementing community pharmacists’ perspectives into collaboration between community pharmacists and hospital pharmacists, a tracing report model incorporating the Common Terminology Criteria for Adverse Events (CTCAE) ver. 5.0 has been created. And, a regimen of drugs and operation describing necessary supportive care has been published in The Cancer Institute Hospital of JFCR website. As a practice of patient safety management at pharmacies, we are working on the standardization of questionnaire criteria to assess the severity of adverse medication reactions in cancer patients and the measurement of health-related quality of life using EuroQol 5 dimensions 5-level (EQ-5D-5L), introduced with cooperation of universities, hospitals, and pharmacies. As medical care is advancing day by day, especially in cancer medication therapy, patient safety management by pharmacists becomes essential, when dealing with the complexity of administration schedule and the wide variety of side effects. For patient safety management, community pharmacists need to practice with pharmaceutical and medical knowledge, and have skills to acquire and convey information, with a researcher’s perspective.

As a patient safety management practice in outpatient cancer drug therapy at community pharmacies, continuous follow-up after the dispensing of medication is required. In 2013, QOL Pharmacy Kohoku and its affiliated stores started the “Telephone Follow-up for Cancer Patients” program, which utilizes telephones and information communication devices to communicate with patients and provide information to hospitals. Specifically, follow-up, including phone calls, is used to ascertain medication status and side effects before the next visit to the hospital, and feedback is provided to the prescribing source using trace reports. In some cases, this initiative has led to an early detection of side effects, reduction in the usage of anticancer drugs, and enhancement of supportive care, leading to patient safety and security. In addition, on August 1, 2021, a new pharmacy accreditation system was launched with two new functional categories, namely “Community Cooperative Pharmacies” and “Specialty Medical Institution Cooperative Pharmacies.” Specialty medical institution-linked pharmacies are defined as pharmacies that can provide specialized and more advanced pharmacological management and dispensing of medications in cooperation with other pharmacies and medical institutions for patients who require specialized pharmacological management, such as in the case of cancer. Following our certification as a specialized medical institution collaborative pharmacy, we intend to continue the efforts we have invested to date and create a community that can assume a prevailing role in patient safety management.

A pharmacist is “a person prepared to formulate, dispense, and provide clinical information on drugs or medications to health professionals and patients.” A pharmacist is one member of the health care team, and he/she plays a key role in providing quality health and pharmaceutical care to the public. Health-related quality of life (HRQoL) is a useful indicator of a patients’ overall health, and it can be estimated by questionnaire survey as patient-reported outcome. The development of an innovative method that extracts HRQoL data from compounding information from pharmacies and pharmacy department in hospital may be useful for a patient-centered medical care. In the near future, pharmacists will have to demonstrate their ability to create value for drug therapy by collecting HRQoL information that corresponds to the national policy of cost-effectiveness. In particular, evaluation of the value of chemotherapy is a problem involving education, clinical techniques, and society, so all pharmacists should work on this as a national topic.

The Faculty of Pharmaceutical Sciences, Kobe Gakuin University has collaborated in clinical research with Kobe City Medical Center General Hospital. In this university–medical institution collaboration, university faculty members discuss clinical problems with on-site pharmacists and doctors, and carry out clinical research to resolve these problems. During the coronavirus disease 2019 (COVID-19) pandemic, many patients with COVID-19 were treated at Kobe City Medical Center General Hospital. In February 2020, during the first increase in the number of patients with COVID-19 in Japan, treatment for COVID-19 was not established, and some existing anti-viral drugs, such as favipiravir, were experimentally used for COVID-19 treatment. However, since these drugs were not developed specifically for treating COVID-19, their pharmacokinetics have not been sufficiently studied. In particular, the pharmacokinetics of favipiravir in critically ill patients with COVID-19 was of concern, because critically ill patients have an urgent need for life-saving anti-viral drug treatment. Therefore, we conducted a collaborative clinical study to evaluate the pharmacokinetics of favipiravir in patients with COVID-19. The blood concentration of favipiravir in patients with COVID-19 at Kobe City Medical Center General Hospital was measured by lipid chromatography-tandem mass spectrometry at Kobe Gakuin University. Population pharmacokinetics analysis was then performed. In this symposium review, we introduce our pharmacokinetic study of antiviral drugs in patients with COVID-19, focusing on the university–medical institution collaboration. We believe collaborative clinical research will be useful for solving clinical issues and ensuring the effectiveness and safety of pharmacotherapies.

The expression of multiple drug transporters and drug-metabolizing enzymes in the small intestine entails a detailed evaluation of the intestinal drug absorption in light of the contribution of these pharmacokinetic-related molecules. The intestinal mucosal damage and barrier disruption caused by diseases and xenobiotics influences health. Therefore, developing models to evaluate drug disposition and mucosal damage in humans is essential. We generated intestinal models from human induced pluripotent stem (iPS) cells and evaluated the availability of the models. The human iPS cell-derived intestinal epithelial cells demonstrated enhanced cellular uptake and multiple efflux transporters. The CYP3A4/5 activity of the human iPS cell-derived intestinal epithelial cells was comparable to that of the human primary enterocytes. Moreover, the correlation between the fraction absorbed (F_a) and apparent permeability coefficient (P_app) of drugs in human iPS cell-derived intestinal epithelial cells was better than in Caco-2 cells, except for the CYP3A4 substrates. Furthermore, we established a method for the differentiation of intestinal organoids from human iPS cells. The budding-like intestinal organoids consisted of various intestinal cells. The organoids demonstrated intestinal mucosal damage caused by tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), the main factors of inflammatory bowel diseases. Furthermore, when the organoids were dissociated and seeded on cell culture inserts, transepithelial electrical resistant values—an index of barrier function—increased gradually. These results demonstrate that human iPS cell-derived intestinal epithelial cells and intestinal organoids could be applied to evaluate intestinal drug disposition and mucosal damage.

There is a growing demand for the implementation of precision medicine. There is an urgent need to move away from one-size-fits-all medicine, in which the treatment is based on the disease name alone, and to implement a precision-medicine approach. Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) require a precision-medicine approach. Asthma and COPD are heterogeneous disorders with various phenotypes. In order to characterize the pathological features of a patient, it is important to analyze not only the phenotype, but also the molecular mechanisms underlying the clinical features, called endotypes. It is crucial to customize the treatment of the disease according to both the phenotype and endotype. Therefore, developing biomarkers enabling treatment stratification is essential to the practice of precision medicine. This approach of finding optimal treatment by identifying patient features using biomarkers is known as a treatable-traits approach. We conducted clinical and basic studies to identify patients with COPD who could be treated with asthma medications and to identify the pathological features of patients with COPD and asthma (asthma-COPD overlap: ACO). We identified several blood proteins and microRNAs that have potential for be clinically useful as biomarkers for customizing treatment in patients with ACO.

Changing workplace attitudes toward clinical research is fostered by trial and error providing optimal therapeutic backgrounds and diverse ideas. On the other hand, students have many opportunities to learn while in university, and we hope that they will have hopes to contribute to team medicine and community health care, and still develop a research mindset. As one of the ways to achieve these objectives, students can be exposed to clinical research from an early point by sharing information with pharmacists and other professionals in the clinical field and working on their research projects. Our laboratory has been engaged in community health care challenges through collaborations with municipal hospitals and pharmacies in the region. In this context, we will introduce the connection between students and post-graduate education based on examples of graduation research worked on with pharmacists and professors of various professions. 1) Retrospective Study of Nutrition Risk Assessment Using Nutrition Tools: A research case study of a multidisciplinary collaboration on nutrition screening using three different nutrition assessment tools to clarify how nutritional endpoints affect nutrition risk assessment. 2) Validation of Causes and Countermeasures for Falls Using a Falls Assessment Score Sheet: Falls of the elderly in community health care. A case study of verifying fall prevention measures from the perspective of two factors: geriatric syndrome and multiple drug administration.

This review reflects on my 43 years of teaching and research at Showa Pharmaceutical University (SPU), Japan. As an English teacher, I have struggled with the question, “How can I, with no specialized knowledge of pharmacy, support pharmacy students and pharmacists?” During my career, a flood of reforms swept through English, university, and pharmacy education. I was able to survive thanks to the support of my teachers, colleagues, students, and alumni. I graduated from the Literature Department at Rikkyo University and joined the foreign language office at SPU in 1979 and started research in English literature at Rikkyo the following year. In 1995, I was promoted to lecturer at SPU and assigned to teach the first and second-year students English. I joined the English for specific purposes (ESP) Study Group of the Japan Association of College English Teachers to promote English education grounded in specialized education, and in 2000 was in charge of the pharmaceutical section of the survey “The Current Status of ESP Education at Universities.” In 2005, I was promoted to Associate Professor and in 2007, I joined other teachers in founding the Japan Association of Pharmaceutical English (JAPE), aiming to develop English teaching materials that fit the core curriculum of the six-year pharmacy education introduced in 2006. By 2021 we had published nine textbooks on pharmaceutical English. In 2006, I introduced drama lessons for first year students, to develop their social awareness of their colleagues. These approaches enabled my students to give presentations at academic conferences.

Although the need for homecare medicine for children is increasing in Japan, few studies have focused on the role of pharmacists in this area. The purpose of the present study was to clarify the practice process of pharmacists in pediatric homecare medicine and develop a practice model. Three pharmacists with experience in homecare medicine for children participated in semi-structured interviews. The data were analyzed using the modified-grounded theory approach (M-GTA). The analysis generated 8 categories and 21 concepts. The practice of pharmacists in homecare medicine for children is the pharmacotherapy management process, and it aims at “enabling the transition from hospital to home for children and continuity of their homelife with family” in collaboration with other professions. Above all, the two concepts of “optimization of prescription and device selection to enable the hospital-to-home transition” and “optimization of prescription and device selection for ensuring patient safety” form the core of clinical decision making in the pharmacotherapy management process. By integrating these two optimization concepts, the transfer of patients to home can be undertaken smoothly, leading to safer pharmacotherapy in the lives of patients and their families. Furthermore, pharmacists considered clinical decision making from two perspectives: “the child’s growth-based approach” and “homelife-based approach.” The foundation of these practice processes comprised “professional responsibilities” and “consideration of families’ feelings.”

The Japanese Pharmacopoeia (JP) is an official normative publication for establishing the authenticity and properties and maintaining the quality of pharmaceutical products in Japan. The JP is revised every five years and partially revised in order to respond to the progress of science and technology, the demand for medical care, and international harmonization. Thus, “Internationalization of the JP” is one of the most important issues to address for the revision of the JP, which is also referred to the basic principles for the preparation of the JP 19th edition. For instance, the incorporation of the test methods that have been used in other pharmacopeias, such as the European Pharmacopoeia (EP) and the United States Pharmacopeia (USP), into the JP is one of promising approaches. From this perspective, we have recently reported changes in test methods, establishment of a quantitative test method for the JP-listed clonidine hydrochloride as well as lorazepam from using a potentiometric titration method to using HPLC method. As our ongoing study to change test methods for internationalization, we selected sodium cromoglicate and trihexyphenidyl hydrochloride. Each pharmaceutical product is analyzed using a potentiometric titration method as listed in the 18th JP; however, both the EP and the USP use HPLC method for quantitative analysis of these drugs. In this study, we synthesized the related impurities of sodium cromoglicate and trihexyphenidyl hydrochloride listed in the EP and determined their purities using quantitative NMR. The separation conditions of these compounds were examined using HPLC and simultaneous analyses were performed.

The model core curriculum for pharmacy education and professional standards for pharmacists established by the Japan Pharmaceutical Association aim to inculcate knowledge and skills on basic life support (BLS) and ensure that pharmacy students are well equipped with knowledge on BLS. In this study, pharmacy students were enrolled in the PUSH course, a BLS training course for citizens, and a questionnaire survey was conducted before and after the course to evaluate the change in students awareness about BLS and overall satisfaction with the course. The participants enrolled for the course were fourth-year students from the School of Pharmacy, Hyogo Medical University, who consented to participate in the study. A total of ninety-nine participants were included in this study. After the completion of the course, the participants displayed greater confidence, preparedness, and willingness to teach BLS, and decreased anxiety about BLS. Factor analysis revealed four factors based on the questionnaire answers before the course, while three factors were extracted based on the answers after the course. Lack of confidence in BLS, extracted as one of the factors before the course was inverted and gave rise to a new factor. Some participants displayed increased awareness about BLS after completion of the PUSH course. Hierarchical cluster analysis before and after the course divided respondents into three groups. The results showed that lesser number of participants displayed anxiety over BLS after the course. The results also indicated high levels of satisfaction among the participants after the completion of the PUSH course.

Since the early 2000s, Japan has been frequently noted as being the only country among about 20 major countries where the publication of academic papers has stagnated. During this period, there have been major changes especially with regards to the Japanese pharmacy schools, such as the shift to a six-year schooling system and the rapid increase in the number of private pharmacy schools. However, few studies have focused on academic productivity specifically among pharmacy schools. Therefore, this study analyzed the outputs associated with the publication of peer-reviewed scholarly articles in Scopus search engine per faculty member in pharmacy schools nationwide in 2020. Professors, associate professors, and lecturers were considered as faculty members. The average number of papers published per the faculty member was 3.13 for national and public universities and 1.15 for private universities, with a significant difference between these universities. Dividing the pharmacy schools of private universities into schools established in and after 2003 and schools established before that, the production coefficient of the former was 0.98 and that of the latter was 1.33. Newly established pharmacy schools were thus found to be slightly less productive in terms of published papers than traditional schools. The paper productivity of private university pharmacy schools is stagnant; the increase in the number of private schools that have adopted a six-year schooling system has contributed to large extent to the creation of clinically competent pharmacists, but it has also brought to light concerns related to the decline in basic research capabilities of Japanese pharmaceutical academia.