The implementation of antimicrobial stewardship (AS) is an important issue that pharmacists should promote through cooperation with physicians and other medical professionals. A core strategy for AS is “proactive intervention and feedback” on antimicrobial prescriptions. We evaluated the AS program to optimize antimicrobial chemotherapy in patients with positive blood cultures. For patients with bacteremia, the rate of bacterial disappearance significantly improved in cases in which the feedback based on the antimicrobial susceptibility testing results by the AS team was accepted than in cases in which it was not. Additionally, we attempted to conduct therapeutic drug monitoring for important antimicrobial agents, such as colistin (anti-multidrug-resistant Pseudomonas aeruginosa agent), vancomycin, daptomycin (antibiotics for methicillin-resistant Staphylococcus aureus), and voriconazole (antifungal drug), to optimize dosage and administration for efficacy and safety. For daptomycin, we found a correlation between plasma through concentration and musculoskeletal toxicity in a clinical study. Moreover, direct toxicity to human skeletal cells was observed in an in vitro study using human myoblast cultures. Overall, the results of these studies indicate that further clinical research on AS may aid the improvement of patient efficacy and safety.

The adverse chapter of cancer chemotherapy negatively impact QOL, and pharmacists play a key role in improving QOL by providing optimal drug therapy through pharmaceutical interventions. Although outpatient cancer chemotherapy is now common, the impact of pharmaceutical interventions from a QOL perspective has not been thoroughly studied. Therefore, this study investigated the impact and cost–effectiveness of pharmaceutical interventions on QOL using the EuroQol 5 Dimension (EQ-5D) and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD). The study was conducted between 2013 and 2015 on 39 patients who underwent their first outpatient chemotherapy for breast cancer at Gifu Municipal Hospital. The results showed that pharmaceutical interventions improved social relationship QOL in patients experiencing fatigue during the first cycle and enhanced psychological QOL in patients with adverse events of nausea during the second cycle. Furthermore, the maximum incremental cost–effectiveness ratio (ICER) was found to be 1.3 million yen per quality-adjusted life years (QALY) according to cost utility analysis. The pharmaceutical interventions by pharmacists in outpatient cancer chemotherapy improve QOL, and the ICER remains well below the Japanese threshold, signifying clear medical and economic benefits.

Organobismuth compounds have been used in various areas of science, like biology and organic synthesis, because they are normally nontoxic and exhibit unique properties. Bismuth induces metallothionein production and is known to exhibit thiophilicity. However, few reports on the reactions between bismuth and sulfur compounds exist. This article reviews studies on the reactivity of bismuth (III and V) with sulfur compounds. A simple approach for the reaction of azole-2-thiones, which contains a heterocyclic ring, with triaryl bismuthines in the presence of a copper catalyst affords the S-arylated coupling product. When a palladium catalyst is used instead of a copper catalyst, desulfinative C–C bond formation occurs. These reactions indicate that trivalent bismuth compounds can be used as novel aryl sources. Triphenylbismuth dichloride, an organobismuth (V) reagent, successfully promotes the cyclodesulfurization of thioureas within short reaction times under mild conditions. The reaction affords N-substituted benzoxazol-2-amines in excellent yields. Tafamidis, a drug used to treat transthyretin amyloidosis, can be synthesized using this reaction.

Interindividual differences in the expression and activity of drug-metabolizing enzymes, including cytochrome P450, UDP-glucuronosyltransferase, and esterases, cause variability of therapeutic effectiveness and side effects during drug treatment. Conventional research has focused on transcriptional regulation by transcription factors and nuclear receptors such as aryl hydrocarbon receptor, pregnane X receptor (PXR), constitutive androstane receptor, and hepatocyte nuclear factor 4α, as the major mechanisms causing the differences in the expression of drug-metabolizing enzymes. Recently, we have revealed that adenosine-to-inosine RNA editing and methylation of adenosine at the N⁶ position on RNA, two major types of posttranscriptional modification, play a pivotal role in the regulation of drug metabolism. In addition, switch/sucrose non-fermentable complex, a chromatin remodeler, is required for PXR-mediated transcriptional regulation of drug-metabolizing enzymes. This review article introduces the significance of these epitranscriptomic and epigenetic regulations as factors in determining drug metabolism potency. Further research on this link is expected to lead to a deeper understanding of interindividual differences in the therapeutic effectiveness and side effects of medicines.

Patients with special backgrounds such as organ dysfunction, elderly individuals, children, and pregnant or nursing women in whom the pharmacokinetics of an agent are expected to differ from those observed in the general patient population, are referred to as “special populations.” Administration of drug therapy to these patients warrants close attention to and knowledge of altered pharmacokinetics to design appropriate personalized dosing regimens. In this study, we investigated the effects of hypothermia and renal impairment on drug pharmacokinetics, focusing on tissue distribution. Analysis of the effects of hypothermia on local liver kinetics of drugs revealed decreased activity of drug-metabolizing enzymes and transporters. Furthermore, we investigated in vivo drug pharmacokinetics and observed that blood drug concentrations increased with a decrease in the body temperature. However, the tissue concentration of midazolam (MDZ) remained unchanged even with a decrease in body temperature, which indicates reduced tissue transfer of MDZ. With regard to the effect of renal impairment, blood concentration of MDZ decreased in patients with acute renal failure and increased in those with chronic renal failure. However, MDZ clearance was decreased in patients with chronic renal failure owing to decreased expression of hepatic metabolic enzymes and reduced hepatic blood flow. This study highlights that tissue translocation of drugs differs across special populations and that optimization of drug administration based on the prediction of tissue concentrations is important.

Platelet-activating factor (PAF), a phospholipid mediator, was discovered in 1972 as an inducer of platelet aggregation. Subsequent studies have revealed that PAF has a variety of biological functions, such as its role as a potent proinflammatory mediator. Additionally, PAF regulates the contractile functions of various types of smooth muscle (SM), such as the (1) endothelium-dependent relaxation of vascular SM; (2) contraction and epithelium-dependent relaxation of airway SM; (3) contraction of gastrointestinal SM; and (4) contraction of uterine SM, which occurs more strongly in pregnant females. PAF is produced in platelets, monocytes, neutrophils, and macrophages, which are cells related to thrombus formation and inflammation/immune responses. Furthermore, PAF is produced in various other cells throughout the body. Interestingly, recent studies have focused on the urinary bladder (UB) as a PAF-producing organ since the accumulation of this phospholipid is enhanced in patients with bladder cancer and interstitial cystitis/bladder pain syndrome, especially those who smoke. Therefore, in UB tissue, PAF may play a substantial role as an inducer or enhancer of cancers and inflammatory diseases. However, the effects of PAF on the immediate mechanical activities of UBSM have not been investigated to date. In this regard, we recently discovered that PAF strongly enhances mechanical activities (muscle tone and spontaneous contractile activity) in UBSM tissues isolated from guinea pigs and mice. In this review article, we present our data on these PAF effects together with the possible underlying mechanisms. We also discuss the potential pathophysiological roles of this phospholipid in UB diseases and disorders.

In recent years, virtual reality (VR) technology has garnered attention as an educational tool. It is believed to be beneficial to utilize VR technology for the acquisition of pharmacist skills. Therefore, we developed a VR training tool aimed at acquiring skills in the preparation of pharmaceuticals in preparatory clinical education for pharmacy students. Additionally, we evaluated the effectiveness of the VR training tool by having beginners learn about the preparation of liquid medications through VR materials or existing texts (Tx) and assessing their learning outcomes in subsequent practical exams. The study included 12 participants in the VR group and 10 in the Tx group. For the items “smoothly and rhythmically performing a series of actions or operations,” “aligning the meniscus with eye level during scale confirmation,” “marking lines on the dispensing bottle,” and “placing lines at the appropriate scale on the dispensing bottle,” students in the VR group were significantly more capable in practical application. The time required to prepare the liquid medication was significantly shorter for students in the VR group, with over half of the Tx group students exceeding 10 min and terminating the task. According to the survey results, many students cited VR as a method for acquiring dispensing skills. Based on these results, our developed VR training tool for liquid formulation showed usefulness in teaching practical skills to beginners.

Although odor is an important indicator of herbal medicine quality, an objective odor evaluation method remains undiscovered. Quantitative measurement using previous methods is complicated as Citrus Unshiu Peel (Chimpi) emits an odor when broken. To establish odor evaluation methods for herbal medicines using chimpi as an example, we developed a reproducible method for breaking samples and an objective odor evaluation method using an electronic nose (e-nose). First, an odor-emitting device (OED) was fabricated by modifying a pill cutter, which suppressed the spread of odor components into the room air while cutting the samples. The odor was emitted from chimpi with an OED and measured using an e-nose. The cut length was then measured. The sensor intensity was positively correlated with the cut length (r=0.840–0.927) in the same sample, and the intensity per unit length (INPULTH) calculated from the sensor intensity and cut length enables the comparison of the sensor intensity among different samples. In addition, average d-limonene emission level measured by GC-MS was positively correlated with average INPULTH (r=0.999), which suggests that this OED and e-nose method enables the comparison of the sensor intensity and d-limonene emissions. INPULTH also positively correlated with other seven monoterpenes such as p-cymene, β-myrcene, β-phellandrene, α-pinene, β-pinene, γ-terpinene, and α-terpinolene (r=0.701–0.865). Therefore, monoterpene content can be evaluated by measuring the odor in the same way as d-limonene. In conclusion, we developed a simple odor intensity evaluation method optimized for chimpi to establish an odor evaluation method for herbal medicines.

Poor medication compliance in children can affect treatment efficacy. We examined the impact of a picture book created by pharmacists to improve medication compliance in children. Our study aim was to assess the effects of the pharmacist-created picture book on medication compliance in children and their parents in collaboration with an outpatient pharmacy. This study included 74 children [recovery rate 28/74 (37.8%)] aged 3–6 years and their parents between March 2023 and March 2024. In the item “Have you experienced any difficulties in giving medication to your child?” the proportion of respondents answering, “Always” or “Sometimes” decreased from 78.3% (18/23) to 34.7% (8/23) after reading the picture book (p<0.01). When answering the question “What specific situations have you found challenging when giving medication?” the number of responses decreased from (an average/mean) of 1.5 situations before reading the picture book to 1 situation. Regarding whether guardians felt a greater appreciation for the importance of giving medication to their children after reading the book, 64.3% answered “Yes,” the highest response. A positive correlation (correlation coefficient=0.77, p<0.01) was observed between “Is the child interested in taking the medication?” and “Is the child able to take the medicine? Pharmacists need to raise public awareness of the importance of medication adherence. Since picture books are likely to be repeatedly read aloud, they are considered effective. The results of this study suggest that pharmacist-created picture books may contribute to improving medication compliance in children.