Pharmacological and toxicological assessments of a wide array of chemicals typically involve estimating human clearance through allometric extrapolation of in vivo animal data, using empirical compartmental and physiologically based pharmacokinetic (PBPK) models. Parameters for pharmacokinetic absorption, distribution, and metabolic clearance can be calculated and applied to models that replicate observed plasma drug concentration–time profiles. In patients with genetically impaired cytochrome P450 (P450) enzymes who are prescribed only certain drugs, moderate plasma exposure should be noted as a precaution on drug labels, as genetic variants can cause changes in blood concentrations similar to those caused by drug–drug interactions. For new approach methodologies that do not rely on experimental data, human PBPK model input parameters for various compounds have been effectively estimated using in silico-generated chemical descriptors and machine learning tools to assess internal exposure in humans. Many drug oxidations are facilitated by species-dependent and polymorphic P450s and flavin-containing monooxygenases (FMOs). For instance, in rats, the main oxidation product of thalidomide was deactivated 5′-hydroxythalidomide, along with sulfate and glucuronide conjugates. However, the species-specific teratogen thalidomide induces human P450 3A and is activated by P450 3A through the primary human metabolite 5-hydroxythalidomide, leading to its conjugation with nonspecific proteins. The metabolic capacity of polymorphic FMO3 was evaluated based on urine tests for food-derived trimethylamine N-oxide levels. This pharmacokinetic modeling approach, incorporating polymorphic drug-metabolizing enzyme information, could be applied in clinical settings and during computational data-driven evaluations of potential risks associated with a broad spectrum of chemicals.

We have engaged in clinical practice and pharmaceutical research aimed at the appropriate use of medications. In pharmacist-to-pharmacist collaboration using medication guidance information-sharing documents, it was possible to monitor treatment efficacy and adverse effects through sharing clinical data, or making prescription proposals. Our hospital’s pharmacist services contributed to expanding the calculation of drug management and guidance fees by pharmacists in clinics with beds. The drug interaction that occurred between enteric-coated omeprazole tablets and Maalox^® granules suggested the possibility of an unexpected drug interaction through a mechanism distinct from that reported for fluoroquinolones and Maalox^® suspension. It has been suggested that certain components of black vinegar strongly inhibit P-glycoprotein (P-gp) function in the intestines, potentially enhancing the absorption of P-gp substrates. It has been suggested that aojiru strongly binds to cationic drugs with cyclic structures, significantly reducing their absorption. Based on these findings, we will continue to conduct pharmaceutical research in clinical practice and promote the appropriate use of medications.

In recent years, therapeutic antibodies with various molecular modifications, such as antibody–drug conjugates, glycoengineered antibodies, and bispecific antibodies, have been developed to address unmet medical needs, resulting in increasingly complex and diverse molecular characteristics. Antibody therapeutics are multifunctional molecules capable of binding not only target antigens but also to Fcγ receptors (FcγRs) and complement. To ensure their proper effector functions, exemplified by antibody-dependent cell-mediated cytotoxicity (ADCC), it is essential to identify and appropriately control their quality attributes that influence the effector functions. To date, we have conducted studies on (1) development of novel analytical methods utilizing antibody–FcγR binding affinity, (2) control of characteristics of antibody molecules through peptide conjugation, and (3) establishment of methods for evaluating the higher-order structure of antibodies using spectroscopic and statistical approaches. The molecular mechanism underlying the effector function of therapeutic antibodies and the advanced quality assessment methods developed in this study are expected to contribute to the promotion of development and quality assurance of next-generation therapeutic antibodies that continue to evolve through diverse molecular modifications.

Supramolecular gels are soft materials formed through the self-assembly of low-molecular-weight gelators via noncovalent interactions. Because their molecular structures can be precisely designed, supramolecular gels are promising functional materials with stimuli-responsive properties. This review summarizes our studies on the design and development of supramolecular gels for pharmaceutical applications, as well as the mechanistic elucidation of supramolecular gelation. First, disaccharide-coupled amphiphilic ureas were designed as low-molecular-weight gelators for small intestine-targeted drug delivery systems. Maltose- and lactose-coupled amphiphilic ureas, Mal-Cn and Lac-Cn, were synthesized in three steps. The resulting supramolecular gels showed enzymatic hydrolysis-responsive phase transitions triggered by disaccharidases. In particular, the supramolecular gel formed from Lac-C8 was degraded by β-galactosidase, and the entrapped model drug, Rhodamine 6G, was released as the gel degraded. These results demonstrate the potential of enzymatic hydrolysis-responsive supramolecular gels as drug carriers. Second, the gelation mechanism of a urea-based low-molecular-weight gelator was investigated using high-speed atomic force microscopy. Direct observation revealed that gel-forming fibers grew through repeated elongation and pause phases. A block-stacking model was proposed to explain the intermittent growth of fibers. Through these observations and additional experimental analyses, we elucidated the mechanism of supramolecular gelation.

Sepsis is defined as “a life-threatening organ dysfunction caused by a dysregulated host response to infection” and is one of the most frequent causes of death worldwide. In 2020, the World Health Organization released their first global report on sepsis: “Global Report on the Epidemiology and Burden of Sepsis.” This report recommended inclusion of sepsis in all public health efforts such as national action plans. Bacteria, viruses and fungi can all cause sepsis, but bacteria are the most common cause. Bacterial endotoxin, the major cell wall component of Gram-negative bacteria, triggers massive systemic inflammation and plays a pivotal role in sepsis pathogenesis. Targeting endotoxin has thus long been a major therapeutic strategy for treating sepsis. Sepsis due to Gram-positive bacteria occurs at a similar rate as that for Gram-negative bacteria, but the causative agents of Gram-positive sepsis remain poorly understood. A variety of microbial components trigger distinctive inflammation by acting as pathogen-associated molecular patterns (PAMPs), which are recognized by specific pattern recognition receptors (PRRs) on host immune cells. Due to the often-fast progression of sepsis, rapid and accurate identification of its causative agents is crucial for effective treatment. This review provides an overview of the author’s research for overcoming sepsis.

Dementia is a progressive neurodegenerative condition that severely impairs memory and activities of daily living. In an aging society like Japan, the physical, mental, and economic burdens associated with caregiving and medical expenses are substantial, making it an increasingly serious social issue. This review focuses on Centella asiatica, used in Ayurveda for its memory-enhancing effects, and introduces examples of plant-derived components from traditional medicine applied in drug discovery and preventive medicine. We have fractionated Centella asiatica extracts and identified the active component araliadiol. We have also demonstrated that Centella asiatica extracts and araliadiol exhibit potent cytoprotective effects against oxidative stress and endoplasmic reticulum stress. Furthermore, araliadiol improved drug-induced cognitive impairment. This review summarizes the preventive effects of Centella asiatica extracts and araliadiol against dementia, based on our previous research findings.

Active learning methods, such as team- and problem-based learning, are known to improve students’ learning attitudes and teamwork skills in undergraduate education. This study conducted an experiment that incorporated an escape room (ER) in classes with the aim of improving students’ motivation to learn and knowledge acquisition through collaborative learning. An ER was designed and administered to third-year undergraduate pharmacy students. Students were randomly assigned to a control group (regular lecture focused on knowledge transfer) or an ER group. Both groups completed pre- and post-tests. Learning outcomes and educational usefulness were evaluated using statistical analyses (t-test and chi-squared test) and text mining. The ER group had significantly higher average post-test scores compared with the control group, particularly in terms of new knowledge acquisition. The results of the questionnaire survey, which included free-form responses, indicated improvements in enjoyment, concentration, and motivation to learn. The ER provided opportunities for collaborative, active learning and demonstrated significant benefits in knowledge acquisition and educational usefulness, including increased motivation. These results could be attributed partly to the fact that ER provides a learning experience combining challenge and a sense of accomplishment, leading to a flow-like psychological state. Therefore, ER demonstrates its potential as an effective method of knowledge education in pharmacy education. Future research can clarify the effectiveness of ER by further examining the conditions that maximize the learning benefits of ER, such as the learning effects of review content and its application to other pharmacy-related subjects.

This study aimed to evaluate the drug cost-saving effects of drug vial optimization (DVO) using an anticancer drug compounding robot in a single institution. Robotic preparations, drug costs, and wastage were evaluated from April to July 2022. Cost-saving simulations were conducted assuming same-day or 7-day DVO. From September to December 2022, DVO was performed for paclitaxel, carboplatin, and etoposide, and actual cost savings were evaluated. During the initial period, 2613 doses (42.0%) were prepared by the robot, with a wastage rate of 2.7%. The simulated cost savings were approximately ¥2.8 million (same-day) and ¥7.49 million (7-days). After the introduction of DVO, 291 vials were saved, equivalent to ¥790000. In conclusion, DVO using an anticancer drug compounding robot can reduce anticancer drug wastage and may contribute to drug cost savings in clinical practice.