著者

Toshinori Hirai Ryosuke Yamaga Motoki Kei Keiko Hosohata Toshimasa Itoh

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.11, pp.1742-1748, 2020-11-01 (Released:2020-11-01)

参考文献数

34

被引用文献数

4

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Although hypokalemia is an adverse effect of Yokukansan preparation, especially in geriatric patients, its association with age is unclear. We investigated whether age is a risk factor for hypokalemia. This single-center retrospective cohort study, conducted at Tokyo Women’s Medical University, Medical Center East between June 2015 and May 2019, included patients who received the Yokukansan preparation. The primary outcome was hypokalemia (serum potassium level: < 3.0 mEq/L). A multivariate Cox proportional hazard model was used to determine risk factors, hazard ratio (HR) and 95% confidence interval (95% CI). The cut-off age was also examined. Of 665 patients (median age: 78 years; interquartile range: 68–84 years), 55 (8.3%) developed hypokalemia associated with Yokukansan preparation. Risk factors for hypokalemia were age (HR: 1.013, 95% CI: 1.006–1.021, p < 0.001), dementia (HR: 0.500, 95% CI: 0.357–0.682, p < 0.001), serum albumin level (HR: 0.754, 95% CI: 0.669–0.850, p < 0.001), and daily Yokukansan preparation dose ≥ 7.5 g (HR: 1.446, 95% CI: 1.144–1.850, p = 0.002). The cut-off ages were >75 and >80 years but not 65 years and >70 years. Clinicians should assess risk factors and monitor serum potassium levels to avoid hypokalemia associated with the Yokukansan preparation.

著者

Fumihiro Yoshimura Seitaro Oda Masafumi Kidoh Hidetaka Hayashi Mari Yonemura Shuhei Miyazaki Seiji Takashio Yuki Kuramoto Yoshihiro Asano Kenichi Tsujita Toshinori Hirai

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-23-0480, (Released:2023-08-26)

参考文献数

2

被引用文献数

1

著者

Naoto Kuyama Koichi Kaikita Masanobu Ishii Noriaki Tabata Seitaro Oda Yasuhiro Otsuka Koichi Egashira Yuichiro Shirahama Shinsuke Hanatani Seiji Takashio Yasushi Matsuzawa Eiichiro Yamamoto Toshinori Hirai Kenichi Tsujita

出版者

The Japanese Circulation Society

雑誌

Circulation Reports (ISSN:24340790)

巻号頁・発行日

pp.CR-23-0092, (Released:2023-11-30)

参考文献数

21

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Background: Subclinical leaflet thrombosis occasionally occurs after transcatheter aortic valve implantation (TAVI), but its exact etiology and relationship with thrombogenicity remain unknown.Methods and Results: This study enrolled 35 patients who underwent TAVI. Thrombogenicity was evaluated using a total thrombus-formation analysis system (T-TAS) to compute the thrombus-formation area under the curve (PL18-AUC10and AR10-AUC30). Periprocedural thrombogenic parameters including T-TAS were investigated at pre-TAVI, 2 days, 7 days, and 3 months post-TAVI. Hypoattenuated leaflet thickening (HALT) and maximum leaflet thickness (MLT) were evaluated using contrast-enhanced computed tomography 7 days and 3 months post-TAVI. The associations between thrombogenicity and HALT or MLT were assessed. T-TAS parameters consistently decreased at 2 and 7 days post-TAVI, followed by improvement at 3 months. HALT was detected in 20% and 17% of patients at 7 days and 3 months, respectively, post-TAVI. The median MLT value was 1.60 mm at 7 days and 3 months post-TAVI. A significant positive correlation was observed between the decrease in the AR10-AUC30and MLT at 7 days post-TAVI. Univariate linear regression analysis revealed a decrease in the AR10-AUC30and an increase in the D-dimer level as a significant predictor of MLT deterioration.Conclusions: The findings suggested that a transient decrease in thrombogenicity following TAVI predicts leaflet thrombosis, implying that monitoring thrombogenicity may be useful for predicting progression of leaflet thrombosis.

著者

Toshinori Hirai Hidefumi Kasai Masahiro Takahashi Satomi Uchida Naoko Akai Kazuhiko Hanada Toshimasa Itoh Takuya Iwamoto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.7, pp.948-954, 2022-07-01 (Released:2022-07-01)

参考文献数

35

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Some population pharmacokinetic models for amiodarone (AMD) did not incorporate N-desethylamiodarone (DEA) concentration. Glucocorticoids activate CYP3A4 activity, metabolizing AMD. In contrast, CYP3A4 activity may decrease under inflammation conditions. However, direct evidence for the role of glucocorticoid or inflammation on the pharmacokinetics of AMD and DEA is lacking. The pilot study aimed to address this gap using a population pharmacokinetic analysis of AMD and DEA. A retrospective cohort observational study in adult patients who underwent AMD treatment with trough concentration measurement was conducted at Tokyo Women’s Medical University, Medical Center East from June 2015 to March 2019. Both structural models of AMD and DEA applied 1-compartment models, which included significant covariates using a stepwise forward selection and backward elimination method. The eligible 81 patients (C-reactive protein level: 0.26 [interquartile range; 0.09–1.92] mg/dL) had a total of 408 trough concentrations for both AMD and DEA. The median trough concentrations were 0.49 [0.31–0.81] µg/mL for AMD and 0.43 [0.28–0.71] µg/mL for DEA during a median follow-up period of 446 [147–1059] d. Three patients received low-dose oral glucocorticoid. The final model identified that AMD clearance was 7.9 L/h, and the apparent DEA clearance was 10.3 L/h. Co-administered glucocorticoids lowered apparent DEA clearance by 35%. These results indicate that co-administered glucocorticoids may increase DEA concentrations in patients without severe inflammation.

著者

Toshinori Hirai Chihiro Shiraishi Tomohiro Murata Takuya Iwamoto

出版者

The Pharmaceutical Society of Japan

雑誌

BPB Reports (ISSN:2434432X)

巻号頁・発行日

vol.4, no.5, pp.170-174, 2021 (Released:2021-10-28)

参考文献数

24

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The impact of renal impairment on the drug-drug interaction between azathioprine and allopurinol that causes myelosuppression and hepatotoxicity remains unclear. This case series study investigated adverse effects caused by azathioprine owing to drug-drug interaction considering renal impairment. Patients who started the combination therapy of azathioprine and allopurinol at Mie University Hospital between January 2013 and February 2021 were enrolled. The outcome of adverse events associated with azathioprine was assessed according to Common Terminology Criteria for Adverse Events version 5.0. The Drug Interaction Probability Scale was used to determine the probability of drug-drug interaction. Of the three patients, two were identified as exhibiting drug-drug interaction with the Drug Interaction Probability Scale > 5 points. They experienced grade 3 myelosuppression or hepatotoxicity with fatigue, after initiation of azathioprine (1.28 and 0.44 mg/kg once daily) and allopurinol (50 mg once daily). They received appropriate dose-adjusted allopurinol according to renal function. Additionally, both patients had the estimated glomerular filtration rate < 60 mL/min/1.73 m2. Thus, renal impairment might reduce the excretion of oxypurinol, an active metabolite of allopurinol, which certainly enhances the side effects of azathioprine.

著者

Junji Mochizuki Takeshi Nakaura Mitsuru Matsukura Yoshiki Hata Toshinori Hirai

出版者

The Japanese Circulation Society

雑誌

Circulation Reports (ISSN:24340790)

巻号頁・発行日

vol.3, no.3, pp.184-185, 2021-03-10 (Released:2021-03-10)

参考文献数

1

被引用文献数

1

著者

Takeshi Nakaura Naoki Kobayashi Naofumi Yoshida Kaori Shiraishi Hiroyuki Uetani Yasunori Nagayama Masafumi Kidoh Toshinori Hirai

出版者

Japanese Society for Magnetic Resonance in Medicine

雑誌

Magnetic Resonance in Medical Sciences (ISSN:13473182)

巻号頁・発行日

pp.rev.2022-0102, (Released:2023-01-26)

参考文献数

71

被引用文献数

3

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The application of machine learning (ML) and deep learning (DL) in radiology has expanded exponentially. In recent years, an extremely large number of studies have reported about the hepatobiliary domain. Its applications range from differential diagnosis to the diagnosis of tumor invasion and prediction of treatment response and prognosis. Moreover, it has been utilized to improve the image quality of DL reconstruction. However, most clinicians are not familiar with ML and DL, and previous studies about these concepts are relatively challenging to understand. In this review article, we aimed to explain the concepts behind ML and DL and to summarize recent achievements in their use in the hepatobiliary region.

著者

Takahiko Aoyama Toshinori Hirai Yasuhiro Tsuji Aoi Miyamoto Toshimasa Itoh Takuya Iwamoto Yoshiaki Matsumoto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.1, pp.136-142, 2022-01-01 (Released:2022-01-01)

参考文献数

31

被引用文献数

1

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Warfarin is a representative anticoagulant with large interindividual variability. The published kinetic-pharmacodynamic (K-PD) model allows the prediction of warfarin dose requirement in Swedish patients; however, its applicability in Japanese patients is not known. We evaluated the model’s predictive performance in Japanese patients with various backgrounds and relationships using Bayesian parameter estimation and sampling times. A single-center retrospective observational study was conducted at Tokyo Women’s Medical University, Medical Center East. The study population consisted of adult patients aged >20 years who commenced warfarin with a prothrombin time-international normalized ratio (PT-INR) from June 2015 to June 2019. The published K-PD model modified by Wright and Duffull was assessed using prediction-corrected visual predictive checks, focusing on clinical characteristics, including age, renal function, and individual prediction error. The external dataset included 232 patients who received an initial warfarin daily dose of 3.2 ± 1.28 mg with 2278 PT-INR points (median [range] follow-up period of 23 d [7–28]). Prediction-corrected visual predictive checks carried a propensity for underprediction. Additionally, age >60 years, body mass index ≤25 kg/m2, and estimated glomerular filtration rate ≤60 mL/min/1.73 m2 had a pronounced tendency to underpredict PT-INR. However, Bayesian prediction using four prior observations reduced underprediction. To improve the prediction performance of these special populations, further studies are required to construct a model to predict warfarin dose requirements in Japanese patients.

著者

Toshinori Hirai Ryosuke Yamaga Motoki Kei Keiko Hosohata Toshimasa Itoh

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.1, pp.118-124, 2021-01-01 (Released:2021-01-01)

参考文献数

41

被引用文献数

3

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The time course of acute kidney injury and hypokalemia remains unelucidated. We investigated whether altered renal function impacts hypokalemia and clinical predictors for acute kidney injury in patients who used Yokukansan preparation. We performed a secondary analysis of retrospective observational cohort data from adult patients who started Yokukansan preparation. The study was conducted from June 2015 to May 2019 at Tokyo Women’s Medical University, Medical Center East. The effect of acute kidney injury (>1.5-fold increase from baseline serum creatinine level) or renal function recovery on hypokalemia (serum potassium level <3.0 mEq/L) was investigated. The clinical predictors for acute kidney injury were determined using a multivariate Cox proportional hazard analysis. Out of 258 patients, 12 patients had both outcomes, and all but one patient experienced in the order of acute kidney injury and hypokalemia. Excluding one patient, hypokalemia occurred in 11/34 (32%) patients after acute kidney injury and 27/223 (12%) patients without acute kidney injury (p = 0.005). Hypokalemia occurred in 9/25 (36%) of acute kidney injury with recovery, 2/9 (22%) of acute kidney injury without recovery, and 27/223 (12%) of no acute kidney injury (p = 0.014). Patients with acute kidney injury showed a late onset of hypokalemia compared with those without acute kidney injury (p = 0.001). In 258 patients, multivariate Cox proportional hazard analysis showed that high systolic blood pressure and mean arterial pressure increased the risk of acute kidney injury. Clinicians should remember that hypokalemia developed after acute kidney injury while Yokukansan preparation treatment.