This nationwide survey aimed to evaluate reduction of drug and medical costs due to prevention of serious adverse drug reactions through pharmaceutical inquires by community pharmacist, and investigate relation with iyaku bungyo (separation of dispensing from medical practice) rates. Using the national list of pharmacies, 10% of pharmacies were randomly selected by prefecture and asked to participate in an Internet-based survey. The survey period was 7 days, from July 21 to July 27, 2015. Of the 5575 pharmacies queried, 818 responded to the survey (response rate: 14.7%). The proportion of inquiries to total prescriptions was 2.6%. Among these, the proportion of prescriptions changed in response to inquiry was 74.9%. An estimated 103 million yen was saved by reducing drug costs, and 133 million yen was saved by reducing medical costs due to prevention of serious adverse drug reactions. Comparison of prescription change rates between pharmacies with high and low iyaku bungyo rates indicated that the proportion of prescriptions changed was significantly higher in pharmacies with high iyaku bungyo rates than in those with low iyaku bungyo rates (78.2% vs. 69.9%, p<0.01). The findings suggest that inquiries about prescriptions are useful in ensuring the safety of pharmacotherapy and reducing the cost of healthcare. They also suggest that iyaku bungyo promotes prescription changes through inquiries, leading to proper use of pharmaceutical products.

Background/Aim: Recent experimental studies have reported that leukotriene receptor antagonists (LTRAs) might protect against dementia. However, few clinical studies have examined this in humans. This study assessed whether the use of LTRAs can prevent the onset of dementia in humans. Patients and Methods: A large population-based retrospective cohort study was conducted using a health insurance claims database in Japan, which included patients newly diagnosed with bronchial asthma between 2006 and 2015. Each of these patients that was LTRA user was matched with a randomly selected LTRA non-user according to age, sex, and bronchial asthma diagnostic year. Results: There were 10,471 patients in both the LTRA user and the LTRA non-user group. Using Cox proportional hazards models, a significant reduction in the risk of developing dementia was observed in the LTRA user group compared to the non-user group (adjusted hazard ratio=0.42, 95% confidence interval=0.20-0.87, p=0.019). Conclusion: Our data suggest that the use of LTRAs may prevent the onset of dementia in asthmatic patients.

Background/Aim: High-dose methotrexate (HD-MTX) is widely used to treat osteosarcoma. However, some patients develop hepatic toxicity, leading to dose modification and delays in the scheduled chemotherapy. The present study aimed to identify the risk factors of hepatotoxicity in patients with osteosarcoma. Patients and Methods: We conducted a retrospective study of patients with osteosarcoma treated with HD-MTX between January 2014 and June 2020 at the National Cancer Center Hospital, Japan. The risk factors for MTX-induced hepatotoxicity (≥grade 3) were identified using multivariate logistic regression analysis. Results: The final analysis included 88 courses of 36 patients. Hepatotoxicity occurred in 51 (58.0%) of the 88 courses. Female sex, MTX dose (>10.2 g/m²), and serum calcium concentration (>9.3 mg/dl) were identified as risk factors for HD-MTX-induced hepatotoxicity. Conclusion: Identifying the risk factors of HD-MTX-induced hepatotoxicity may contribute to improvements in the safety and management of HD-MTX therapy.

Background/Aim: High-dose methotrexate is a therapy for acute leukemia, malignant lymphoma, and osteosarcoma. Glycyrrhizin has been used to treat hepatic dysfunction caused by high-dose methotrexate. However, few studies have investigated the interaction between glycyrrhizin and high-dose methotrexate. Materials and Methods: Male Wistar rats were treated with high-dose methotrexate (500 or 1,000 mg/kg) alone, or with co-administration of 100 mg/kg glycyrrhizin. Plasma concentrations of methotrexate, alanine aminotransferase, aspartate aminotransferase, and total bilirubin were measured. Results: At both methotrexate doses, the blood concentration of methotrexate was significantly increased and total clearance was significantly reduced using co-administration of glycyrrhizin compared with methotrexate alone, which led to increased levels of hepatic enzymes. These results suggest that glycyrrhizin significantly increases the plasma level and delays the clearance of methotrexate, resulting in hepatic toxicity. Conclusion: The concomitant use of methotrexate and glycyrrhizin should be considered with caution.

Background/Aim: Glycyrrhizin (GZ) is widely used to treat high-dose methotrexate (MTX)-induced liver dysfunction. However, in a previous in vivo study, we showed that simultaneous administration of both drugs increased the plasma concentration of MTX and exacerbated hepatic injuries. In this study, we investigated the optimal dosing interval in rats to avoid the interaction between high-dose MTX and GZ and to demonstrate the inherent hepatoprotective effect of GZ. Materials and Methods: Male Wistar rats were treated with high-dose MTX (2,000 mg/kg) alone, with concomitant administration of 100 mg/kg GZ or GZ administered 3, 6, and 24 h before MTX administration. Plasma concentrations of MTX, alanine aminotransferase, aspartate aminotransferase, and total bilirubin were measured. Results: The plasma concentration and half-life of methotrexate were significantly increased after concomitant administration of GZ, or when GZ was administered 3 h before MTX administration, compared with MTX alone, increasing hepatic enzyme levels. However, when GZ was administered 6 and 24 h before MTX administration, the levels were not significantly different from those of MTX alone and showed a tendency to decrease MTX-induced liver injury. These results suggest that the pharmacokinetic interaction between GZ and MTX could be avoided and the hepatoprotective effect of GZ could be achieved by an optimal dosing regimen, using the half-life of GZ as an indicator. Conclusion: When using high-dose MTX in combination with GZ, the administration intervals should be considered to avoid unwanted interactions and to achieve the GZ hepatoprotective effect.

Background: Prostate cancer is one of the most common cancers among men worldwide and the fourth most common cause of death. The number of prostate cancer cases and deaths is increasing every year because of population aging. This study aimed to clarify the risk of developing prostate cancer due to fluctuations in Prostate Specific Antigen (PSA) levels in patients without a history of prostate cancer using large medical information data. Results: This retrospective cohort included 1707 male patients aged 60 years or older who had a PSA level measurement date (2-PSA) within 3 months or more and 2 years from the first PSA level measurement date (1-PSA) in the database between 2008 and 2019. We subtracted 1-PSA from 2-PSA and designated patients with a higher 2-PSA than 1-PSA to the “up” group (n = 967) and patients with a lower 2-PSA than 1-PSA to the “down” group (n = 740). By using Cox proportional hazards model, a significant increase in prostate cancer risk was observed in the up group compared with the down group (adjusted hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.21–2.72; adjusted for patient background factors). Subgroup analysis showed that patients with PSA levels < 4 ng/mL had a significantly increased risk of developing prostate cancer if the next PSA level increases by approximately 20% (adjusted HR = 2.94, 95% CI = 1.14–7.58), and patients with PSA levels of 4 ng/mL or higher if the next PSA level is decreased by approximately 20% had a significantly reduced risk of developing prostate cancer (adjusted HR = 0.36, 95% CI = 0.18–0.74), compared to that with no change. Conclusions: This is the first study to clarify the association between PSA variability and risk of developing prostate cancer in patients without a history of prostate cancer. These results suggest that the suppression of elevated PSA levels may lead to the prevention of prostate cancer and that it would be better to perform a biopsy because the risk of developing prostate cancer may increase in the future if the PSA value increases above a certain level.