BPB Reports

2024 - Vol. 7 No. 6

2024 - Vol. 7

Report
γ-Glutamylcysteine, a Glutathione Precursor, Exhibits Higher Thiol Reactivity for Complex Formation with Iron (III) Ions Compared to Glutathione Vol.7, No.6, p.218-222
Ryotaro Tsutsumi , Takuya Yamashita , Misa Muraoka , Kazumasa Hirata , Kazuya Nagano
Received: October 18, 2024
Accepted: October 30, 2024
Released: December 03, 2024
Abstract Full Text PDF[768K]

Glutathione (GSH), the most abundant intracellular thiol compound, protects various cells from metal toxicities by forming complexes with metal ions through the thiol group. γ-Glutamylcysteine (γ-EC), a glutathione precursor, is anticipated to be a functional thiol compound. However, unlike GSH, the characteristics of γ-EC in metal complex formation are largely unclear. In this study, we analyzed the ability of γ-EC to form complexes with various metal ions. 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) assays demonstrated that the reaction ratios between DTNB and γ-EC and GSH were slightly reduced by adding light metal ions, such as K+, Mg2+, and Al3+. These results indicated that γ-EC and GSH exhibit low thiol reactivity and weak complex formation with these ions. In contrast, the reaction ratio was reduced in a concentration-dependent manner by the addition of heavy metal ions, such as Ag+, Cu2+, Zn2+, and Fe3+. Specifically, the reaction ratio in the γ-EC-treated group was significantly reduced by the addition of Fe3+ compared to that in the GSH-treated group. These data indicate that, while γ-EC as well as GSH form the complexes with Ag+, Cu2+, and Zn2+, γ-EC has a stronger interaction with Fe3+ than GSH. In the proposed complex model based on the hard and soft acids and bases (HSAB) principle, GSH theoretically forms unstable nine-membered rings with Fe3+, whereas γ-EC can form more stable six-membered rings, resulting in a strong interaction between γ-EC and Fe3+.

Regular Article
NAMPT Activator P7C3-A20 Protects against Tunicamycin-Induced Cell Injury in C2C12 Murine Myoblast Cells Vol.7, No.6, p.211-217
Naoki Chinen , Wataru Otsu , Yoshiki Kuse , Shinsuke Nakamura , Hideaki Hara , Masamitsu Shimazawa
Received: July 12, 2024
Accepted: October 28, 2024
Released: November 12, 2024
Abstract Full Text PDF[2M]

Endoplasmic reticulum (ER) stress is linked to insulin resistance and several muscle diseases, including myopathies. ER defects are also implicated in skeletal muscle dysfunction associated with aging. Physical contact between the ER and mitochondria is essential for the local transport of materials and effective signal transduction between these organelles. Nicotinamide phosphoribosyltransferase (NAMPT) regulates mitochondrial biogenesis and maintains skeletal muscle function and integrity. Our study aims to investigate the effect of the NAMPT activator P7C3-A20 on tunicamycin-induced ER stress using an in-vitro myoblast cell model. We found that tunicamycin treatment decreased the expression of several mitochondrial proteins, such as NAMPT and the mitophagy regulator PINK1 in C2C12 murine myoblast cells. It also reduced the phosphorylation of Drp1, a master regulator of mitochondrial fission, in C2C12 cells treated with tunicamycin. JC-1 imaging revealed that treatment with P7C3-A20 for 6 h at concentrations of 1, 5, and 10 μM increased mitochondrial potential in C2C12 cells. Moreover, P7C3-A20 ameliorated tunicamycin-induced cell death in a concentration-dependent manner. In conclusion, the NAMPT activator P7C3-A20 can mitigate tunicamycin-induced cell damage in C2C12 murine myoblasts. Activation of NAMPT is a potential novel therapeutic approach for muscle diseases associated with ER stress, such as sarcopenia.

Report
Development and Validation of an HPLC-UV Method for Capivasertib Quantification in Human Plasma Vol.7, No.6, p.206-210
Yoshito Gando , Takeo Yasu
Received: August 02, 2024
Accepted: October 27, 2024
Released: November 08, 2024
Abstract Full Text PDF[585K]

Capivasertib is an oral molecular targeted drug for treating hormone receptor-positive, human epidermal growth factor receptor 2-negative inoperable or recurrent breast cancer with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, AKT serine/threonine kinase 1, and phosphatase and tensin homolog mutations. Moderate intra- and inter-individual variabilities have been reported in the pharmacokinetic study of capivasertib. Furthermore, because capivasertib is a substrate and weak inhibitor of CYP3A4, drug–drug interactions are expected in elderly patients with breast cancer due to the concomitant use of multiple drugs for co-morbidities. These factors suggest that the therapeutic drug monitoring (TDM) of patients receiving capivasertib may improve therapeutic efficacy while decreasing the onset of adverse events. However, to the best of our knowledge, there are no reports on methods to measure the capivasertib concentration in human plasma. Therefore, this study proposes a method for determining the capivasertib concentration in human plasma using HPLC-UV. Following protein precipitation with methanol, capivasertib and pirfenidone (internal standard) were separated using isocratic elution on a C18 column using a mobile phase of 0.5% KH2PO4 (pH 4.5)/acetonitrile in a 73:27 (vol/vol) ratio, pumped at a constant flow rate of 1.0 mL/min. Quantification was performed at 219 nm. The calibration curves were linear over the range of 50–1000 ng/mL. Intra- and inter-day coefficients of variation were less than 10.2%. The assay accuracy ranged from -7.2–2.9%, and the recovery was >93.8%. This simple and cost-effective method may contribute to the TDM of capivasertib in clinical practice.

Regular Article
Survey on the Involvement of Hospital and Community Pharmacists in Outpatient Chemotherapy in Japan Using Medical Reimbursement Data Vol.7, No.6, p.196-205
Mari Iwata , Mika Maezawa , Kohei Shiota , Sakiko Hirofuji , Koumi Miyasaka , Nanaka Ichihara , Yuka Nokura , Moe Yamashita , Kana Sugishita , Tomofumi Yamazaki , Satoshi Nakao , Hirofumi Tamaki , Kazuhiro Iguchi , Mitsuhiro Nakamura
Received: July 13, 2024
Accepted: September 26, 2024
Released: November 08, 2024
Abstract Full Text PDF[1M]

Background: In Japan, measures are being taken to strengthen the cooperation between local hospitals and pharmacies to improve the quality of cancer treatment. Objective: To evaluate the progress of the medical care provision system in terms of the collaboration between hospital pharmacists and community pharmacists in outpatient chemotherapy. Methods: We focused on the Additional Fee for Outpatient Chemotherapy 1 (when anticancer drugs are injected) (A1OC) as an indicator of high-quality medical care, Additional Fee for Enhanced Collaboration (AEC) as an indicator of hospital pharmacist involvement, and Additional Fee for Specific Drug Management Guidance 2 (ASD2) as an indicator of community pharmacist involvement. Using prefecture-specific receipt claims data from NDB Open Data Japan (NODJ) and from e-Stat, we investigated the number of insurance claims made by hospitals and pharmacies for outpatient chemotherapy involving pharmacists and the factors associated with them. Results: The coefficients of determination (R2) for A1OC, AEC, and ASD2 claims with respect to the number of anticancer drugs injected were 0.9960, 0.8298, and 0.7244, respectively. A higher number of claims for ASD2 was observed in prefectures in which the average age of community pharmacists was lower. Conclusion: The number of A1OC claims, which represents the number of times high-quality medical care was provided, suggests that the quality of the facilities for outpatient chemotherapy delivery systems varies little between prefectures. The involvement of hospital pharmacists varied by region more than A1OC did, and the involvement of community pharmacists varied even more. Reducing these regional differences is necessary to standardize the quality of outpatient cancer chemotherapy in Japan. Our study findings indicate the need for promoting the further involvement of community pharmacists with patients and their collaboration with hospital pharmacists to prevent adverse effects and enhance the quality of life of patients undergoing outpatient chemotherapy. Through such activities, the local collaborative efforts and reimbursement requirements may be improved.

Regular Article
Patient Characteristic for Using Personalized Estimated Glomerular Filtration Rate in Kidney Function Assessment Vol.7, No.6, p.190-195
Madoka Itano , Takayoshi Maiguma
Received: August 06, 2024
Accepted: October 20, 2024
Released: November 08, 2024
Abstract Full Text PDF[705K]

In many medical institutions, standardized eGFR, which is based on generalized body surface area, is used for drug dosing evaluations. This can lead to overdosing. This study aimed to investigate the discrepancy between personalized eGFR and standardized eGFR and to identify indicators necessary for pharmacists to perform appropriate pharmacotherapy. From October 2022 to February 2023, the study targeted patients aged 18 years and older who continuously visited the Saera Pharmacy Kurashiki. Among the 347 participants, a significant discrepancy of 6.3 mL/min was observed between personalized eGFR and standardized eGFR (p < 0.001). Factors predicting an eGFR discrepancy of 10 mL/min or more were identified as follows: for males, a serum Na level below 140 mEq/L (area under the ROC curve: AUC = 0.656), and for females, a BUN level below 13 mg/dL (AUC = 0.647). Recognizing that patients with these factors are at risk of inaccurate renal function assessment, it is considered beneficial for pharmacists to prioritize obtaining height and weight measurements to ensure appropriate dosing of renally excreted drugs.

Regular Article
Changes in Regional Medical Collaboration System and Functions in Community Pharmacy Before and After the Enforcement of the Amended Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices in Tokyo Vol.7, No.6, p.183-189
Daiki Katsuta , Yuki Ohashi , Minami Kamimura , Tetsuya Yamada , Koichi Masuyama , Kunihiko Kitagaki
Received: August 02, 2024
Accepted: October 15, 2024
Released: November 08, 2024
Abstract Full Text PDF[1M]

Over the past few decades, the number of older adults in desperate demand of social support is inevitably increasing with an aging population. Thus, there is a need for a social framework that can improve the quality of life of older adults. In Japan, where the population faces a super-aging society, the aim is to establish a community-based integrated care system that supports the elderly throughout the community. In August 2021, the Japanese government partially amended the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices to expand the flexible healthcare provision, which forms the basis of that system. This amendment encourages patients to choose pharmacies that better meet their needs by establishing a framework for publicly certifying pharmacies that play essential roles in community healthcare, including home healthcare, and pharmacies that can provide specialized medical care. However, the actual effects of the intervention remain unclear. Thus, we explored changes in efforts related to regional medical collaboration and functions in community pharmacies before and after the enforcement of the amended Act. Our survey revealed that the amendment increased the stockpiles of generic medicines at each pharmacy without a clear increase in the number of employees. Additionally, there was an across-the-board improvement in the provision of information to other medical providers and patients. These results indicated that the amendment to the Act directly or indirectly promoted a shift from conventional pharmacy to a more patient-oriented approach.