論文 - 松元　一明

Evaluation for optimal dosing of vancomycin in patients with different physical types

Hashimoto M., Iketani O., Ichinose N., Enoki Y., Taguchi K., Uno S., Uwamino Y., Hasegawa N., Matsumoto K.

Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy）  25 （ 9 ） 735 - 737 2019年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1341321X

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© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases The sufficient dose to obtain an optimal trough concentration of vancomycin (VCM) in patients with non-standard physical types remains controversial. In this study, we examined the relationship between the dose and physical type in patients in whom an optimal trough concentration was obtained among VCM-treated patients. We retrospectively investigated the dose of VCM and physical type in patients treated with VCM between January 2012 and January 2017 at two medical institutions (n = 272). The physical type was classified using the body mass index (BMI). Patients with a BMI of <18.5 kg/m 2 were assigned to the lean group, those with a BMI of 18.5–24.9 kg/m 2 were assigned to the standard group, and those with a BMI of ≥25 kg/m 2 were assigned to the obesity group. The mean doses of VCM per time (mg/kg) to achieve the target trough concentration of VCM, 15–20 μg/mL, were 19.8 ± 4.3, 16.5 ± 3.7, and 13.7 ± 2.7 mg/kg in the lean, standard, and obesity groups, respectively. The dose per time to achieve the target trough concentration decreased significantly in association with an increase of BMI. The upper limit of the recommended dose (15–20 mg/kg) or higher in lean patients, and the lower dose in obese patients than the recommended dose might be appropriate to achieve the target trough concentration when we calculated the dose per time based on actual body weight.

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Experimental verification of factors influencing calcium salt formation based on a survey of the development of ceftriaxone-induced gallstone-related disorder

Ito R., Yoshida A., Taguchi K., Enoki Y., Yokoyama Y., Matsumoto K.

Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy）  25 （ 12 ） 972 - 978 2019年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1341321X

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© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Ceftriaxone (CTRX) forms salts with calcium (Ca) in the gall bladder and bile duct, and induces the formation of gallstones. In this study, factors of CTRX-induced gallstone formation were extracted from the results of a retrospective survey using the Japanese Adverse Drug Event Report (JADER), and the causal relationship between the factors and gallstone formation was investigated. From JADER, 136 patients who developed ‘gallstone-related disorder’ with CTRX as a suspected drug were extracted. The incidence of gallstone-induced adverse effects was high in patients treated with CTRX at a dose exceeding the normal daily dose and in children younger than 10 years old, suggesting that CTRX at a high level is a factor for gallstone formation. Thus, after mixing CTRX and Ca2+ at different concentrations under different pH condition, the number of particles in the solutions was measured using a Coulter counter. As a result, the number of minute particles significantly increased at all pH values when Ca2+ and CTRX were mixed at a concentration of 10 mEq/L or higher and 1.5 g/L or higher, respectively. At pH 6.5 or 7.0, visible crystals were detected when 25 mEq/L of Ca2+ and 2.0 g/L of CTRX were mixed. Based on these findings, attention should be sufficiently paid to the development of ‘gallstone-related disorder’ in pediatric patients and in patients treated with CTRX at a dose exceeding the normal dose. Furthermore, gallstone formation and growth may be promoted when CTRX and Ca2+ coexist at high concentrations under low pH conditions.

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Age-associated theophylline metabolic activity corresponds to the ratio of 1,3-dimethyluric acid to theophylline in mice

Kuroda Y., Taguchi K., Enoki Y., Matsumoto K., Hori S., Kizu J.

Biological and Pharmaceutical Bulletin （Biological and Pharmaceutical Bulletin）  42 （ 8 ） 1423 - 1427 2019年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09186158

　概要を見る

© 2019 The Pharmaceutical Society of Japan. Age is known as one of influencing factor for theophylline (TP)-metabolizing capacity. In a previous our study, the ratio of TP and its major metabolite 1,3-dimethyluric acid (DMU) in serum (DMU/TP) is a useful index to estimate TP-metabolizing capacity, and this value markedly increased by influencing factor, such as the history of smoking. However, it is unknown whether DMU/TP values in serum reflect age-associated changes of TP-metabolizing capacity. In this study, the effect of age on the DMU/TP values in serum were investigated using mice of different age due to the limited blood sampling in human. The concentrations of TP and its metabolites in mouse serum were simultaneously measured using HPLC. As observed in human serum, serum TP concentrations were closely correlated with DMU concentration in mice, which indicates that the DMU/TP ratio is a good indicator of TP metabolic ability in mice. When TP was administered subcutaneously in 2?8-week-old mice, age-associated changes in the DMU/TP ratio in mice were observed. In conclusion, age-associated changes in TP-metabolizing capacity can be estimated by the DMU/TP ratio in serum.

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Clostridioides（Clostridium）difficile感染症診療ガイドライン.

國島広之, 大毛宏喜, 鈴木広道, 中村敦, 松元一明, 三鴨廣繁, 森伸晃, 森永芳智, 栁原克紀, 山岸由佳, 吉澤定子.

感染症学雑誌 92   819 - 854 2018年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0387-5911

Oral vancomycin versus metronidazole for the treatment of Clostridioides difficile infection: Meta-analysis of randomized controlled trials

Igarashi Y., Tashiro S., Enoki Y., Taguchi K., Matsumoto K., Ohge H., Suzuki H., Nakamura A., Mori N., Morinaga Y., Yamagishi Y., Yoshizawa S., Yanagihara K., Mikamo H., Kunishima H.

Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy）  24 （ 11 ） 907 - 914 2018年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1341-321X

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© 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases At present, vancomycin (VCM) and metronidazole (MNZ) are used for the first-line standard treatment of Clostridioides difficile infection (CDI). However, their differential use has not been sufficiently investigated. In this study, a meta-analysis on differences in the efficacy for CDI between VCM and MNZ was performed. Reports of randomized controlled studies using VCM or MNZ to treat CDI were surveyed. Meta-analysis was performed using the Mantel-Haenszel method and random-effects model, and the risk ratio and 95% confidence interval were calculated. Excluding overlapping reports, 1043 reports were extracted and 5 randomized controlled studies were extracted. There was no difference in therapeutic effects for CDI between VCM and MNZ (RR = 1.08, 95% CI (0.99–1.17), p = 0.09, I2 = 37%). On subgroup analysis by the severity, there was no difference in the clinical effects for CDI between VCM and MNZ in non-severe cases (risk ratio: 1.09, 95% confidence interval: 1.00–1.19, p = 0.06), but the clinical effects of VCM were significantly higher than those of MNZ in severe cases (risk ratio: 1.19, 95% confidence interval: 1.02–1.39, p = 0.03). No significant difference was noted in the recurrence rate, incidence of adverse event, time to exhibit therapeutic effects, or judgment of the bacteriological effects. As the therapeutic effects of VCM were superior in severe CDI cases, VCM should be considered first in severe cases.

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Pharmacokinetic and pharmacodynamic studies of pregabalin suppositories based on pharmacological research

Yajima R., Matsumoto K., Yokono K., Watabe Y., Enoki Y., Taguchi K., Ise Y., Katayama S., Kizu J.

Journal of Pharmacy and Pharmacology （Journal of Pharmacy and Pharmacology）  71 （ 5 ） 746 - 752 2018年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2042-7158

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© 2018 Royal Pharmaceutical Society Objectives: As commercially available pregabalin preparations are limited to oral administration, it is impossible to use it as an adjuvant analgesic for neuropathic cancer-related pain in terminally ill cancer patients with oral feeding difficulties. The objective of this study was to develop a pregabalin suppository to be available at hospitals. Methods: Pregabalin suppositories were prepared using bases comprising six different compositions of Witepsol H-15, Witepsol S-55, and Witepsol E-75. The suppository release test and stability test were performed in vitro. The pharmacokinetics and pharmacodynamics of the suppositories were assessed in rats. Key findings: In the in vitro releasing test, the pregabalin suppositories with H-15, H-15 : S-55 = 1 : 1, H-15 : S-55 = 2 : 1, H-15 : S-55 = 1 : 2 released approximately 100% of the pregabalin within 180 min. Among these pregabalin suppositories, only the suppository with H-15 : S-55 = 2 : 1 demonstrated an equivalent AUC 0−∞ with the oral administration group. Consistent with the results of the pharmacokinetic study, the pregabalin suppository with H-15 : S-55 = 2 : 1 exhibited antinociceptive effects. In addition, the pregabalin suppository with H-15 : S-55 = 2 : 1 was stable for 12 weeks when refrigerated with light shielding. Conclusions: The pregabalin suppositories prepared in this study may be applicable for pain control for terminally cancer ill patients with oral feeding difficulties.

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Stability of benzylpenicillin potassium and ampicillin in an elastomeric infusion pump

Nakamura T., Enoki Y., Uno S., Uwamino Y., Iketani O., Hasegawa N., Matsumoto K.

Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy）  24 （ 10 ） 856 - 859 2018年10月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1341-321X

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© 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Some infectious diseases, such as infective endocarditis, osteomyelitis, and abscesses, require treatment with long-term intravenous antimicrobial treatment. Therefore, the patient is required to stay in the hospital to receive therapy, which lowers their quality of life. Establishing an outpatient parenteral antimicrobial therapy (OPAT) by continuous infusion pump is desired in Japan to overcome these issues. However, the 24-h stability of antimicrobial agents dissolved in infusion solutions is unclear. Thus, we investigated the stability of antimicrobial agents in five different infusion solutions in a clinical setting. Benzylpenicillin potassium (PCG) and ampicillin (ABPC) were dissolved separately in five different infusion solutions and kept at 25 or 31.1 °C for 24 h. The residual ratios were determined by high-performance liquid chromatography (HPLC). Dissolved PCG in acetate ringer solution remained stable for 24 h at temperatures of 25 and 31.1 °C (101.7 ± 1.4% and 92.9 ± 1.3%, respectively). In addition, the PCG solution did not adsorb onto the elastomeric infusion pump after 24 h at 31.1 °C. PCG dissolved in acetate ringer solution was also stable for 10 days after being kept in an elastomeric infusion pump at 4 °C (99.7 ± 0.5%). ABPC was unstable in all of the tested infusion solutions and temperatures. Based on our results, PCG in acetate ringer solution can be used in OPAT with continuous infusion pumps.

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Development of HPLC with fluorescent detection using NBD-F for the quantification of colistin sulfate in rat plasma and its pharmacokinetic applications

Ouchi S., Matsumoto K., Okubo M., Yokoyama Y., Kizu J.

Biomedical Chromatography （Biomedical Chromatography）  32 （ 5 ） e4167 2018年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1099-0801

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Copyright © 2017 John Wiley & Sons, Ltd. Colistin sulfate, composed of a mixture of colistin A sulfate (CLA) and colistin B sulfate (CLB), is available for treating life-threatening infections caused by multidrug-resistant Gram-negative bacteria. In this study, the CLA and CLB were quantified separately. Colistin sulfate was extracted from rat plasma with a solid-phase extraction C18 cartridge and reacted with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), and the fluorescent derivatives were subjected to reversed-phase high-performance liquid chromatography analysis and used to investigate the pharmacokinetics of CLA and CLB in rat plasma. The recovery rates of CLA and CLB were 41.2 ± 4.4 and 45.5 ± 3.1%, respectively. The recovery rate calculated from the total area of CLA and CLB was 43.9 ± 3.6%. When 2 mm NBD-F and 10 mm boric acid buffer (pH 9.5) were added to colistin sulfate, the highest recovery rate was obtained. The best heating time was 5 min at 60°C. The lower limits of quantification for CLA, CLB and the total area of CLA and CLB were 0.05, 0.05 and 0.1 μg/mL; the coefficients of variations were 13.5, 14.5 and 14.1%, respectively. This method was found to have acceptable linearity, precision and accuracy, and has been successfully applied to a pharmacokinetic study in rat plasma.

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一包化調剤薬の鑑査業務における刻印錠と両面印字錠の比較.

松元一明, 大森栄, 石井伊都子, 川久保孝, 神田博仁, 鈴木貴明, 横山威一郎, 中澤一純, 木津純子.

日本病院薬剤師会雑誌 （(一社)日本病院薬剤師会）  54 （ 4 ） 433 - 439 2018年04月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1341-8815

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刻印錠と両面印字錠の一包化を行い、薬剤師と薬学部学生を対象に、調剤薬鑑査における鑑査時間、調剤ミスの発見の有無についてタイムスタディを実施し、その後、アンケートを行った。刻印錠の鑑査に、学生(40名)、薬剤師(98名)は平均517.2秒、505.6秒を要し、両面印字錠の平均298.9秒、277.5秒と比較して有意に長かった(p<0.001)。アンケートの結果、刻印錠では、"大変やりにくい"、"やりにくい"との回答が82.6%、両面印字錠では、"大変やりやすい"、"やりやすい"との回答が91.2%得られた。"鑑査の速さ"、"鑑査のしやすさ"、"鑑査の正確性"は71.7%、92.8%、89.9%が、両面印字錠のほうがよいと回答した。今後増え続けると思われる一包化の鑑査業務において、両面印字錠は、鑑査業務の負担軽減に貢献できるものと考える。(著者抄録)

Dosing optimization of meropenem based on a pharmacokinetic analysis in patients receiving hemodiafiltration and an in vitro model

Yokoyama Y., Nishino K., Matsumoto K., Inomoto Y., Matsuda K., Nakamura R., Yasuno N., Kizu J.

Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy）  24 （ 2 ） 92 - 98 2018年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1341-321X

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© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases The purpose of this study was to estimate the in vivo pharmacokinetics of meropenem during intermittent-infusion hemodiafiltration (I-HDF) and clarify its optimal dosage and dosing interval in patients receiving I-HDF. The clearance of meropenem by online hemodiafiltration (OL-HDF) and I-HDF was predicted using an in vitro system and assessed to establish whether the results obtained are applicable to clinical cases. In the in vivo study, the mean volume of distribution (Vd), non-I-HDF clearance (CLnon-I-HDF), and I-HDF clearance (CLI-HDF) were 15.80 ± 3.59 l, 1.05 ± 0.27 l/h, and 5.78 ± 1.03 l/h. Dosing regimens of 0.25 g once daily for a MIC of 8 μg/ml and of 0.5 g once daily for a MIC of 16 μg/ml achieved 40% T > MIC. In the in vitro and in vivo studies, observed CLHDF was similar to predictive CLHDF (= Cf/Cp × (QD + QSUB)). In conclusion, adjustments to the dose and interval of meropenem were developed based on the presumed susceptibility of pathogens to meropenem in patients receiving I-HDF. We suggest 0.5 g once daily as an appropriate regimen for empirical treatment.

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Analysis of Adverse Drug Events in Pulmonary Mycobacterium Avium Complex Disease Using the Japanese Adverse Drug Event Report (JADER) Database

Namkoong H., Takahashi Y., Ishii M., Asakura T., Suzuki S., Kamata H., Yagi K., Betsuyaku T., Matsumoto K., Kizu J., Hasegawa N.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 197 2018年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1073-449X

自動車運転に影響を及ぼす医薬品に対する病院薬剤師の対応.

松元一明, 市川楓子, 黒田裕子, 木津純子.

日本病院薬剤師会雑誌 53   1161 - 1167 2017年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1341-8815

Factorial analysis of hepatitis B virus reactivation-induced hepatitis B using JADER.

Ayako Hara, Kazuaki Matsumoto, Yuta Yokoyama, Junko Kizu.

BIOLOGICAL & PHARMACEUTICAL BULLETIN （PHARMACEUTICAL SOC JAPAN）  40 （ 6 ） 782 - 788 2017年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0918-6158

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Hepatitis B caused by chemotherapy- and immunosuppression-associated hepatitis B virus reactivation is likely to become fulminant, and a high mortality rate has been reported. In this study, using the Japanese adverse drug event report database (JADER), factorial analysis of patients who developed hepatitis B as an adverse event was performed. The number of reported cases of hepatitis B during the survey period was 781 and 185 of them (24%) died. Rituximab and prednisolone were administered to many cases (233, 216 cases, respectively), and the reporting odds ratios were high (65.35, 13.40, respectively), suggesting their strong association with the development of hepatitis B. Regarding the onset time, rituximab-induced hepatitis B developed within one year after administration in 83%, being a high frequency. Prednisolone-induced hepatitis B developed even after one year in 36%. Since prednisolone is used to treat rheumatoid arthritis at a dose &lt;= 10mg/d, the patients were divided based on the prednisolone dose into the groups treated at &gt;10 and &lt;= 10 mg/d, and the onset time was investigated in each group. The median onset time was 113 and 330d, respectively, showing a significant difference. On time-to-event analysis using the Weibull distribution, rituximab was classified as the early failure type, and prednisolone and methotrexate for rheumatoid arthritis were classified as the wear out failure type. These findings are important information which may lead to early discovery of and taking actions against hepatitis B being helpful for providing appropriate medical care.

ラモトリギンの医薬品副作用データおよび医薬品副作用被害救済給付決定情報の調査解析.

横山雄太, 黒田裕子, 安藤剛, 松元一明, 木津純子.

日本病院薬剤師会雑誌 53   283 - 289 2017年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1341-8815

抗菌薬のTDM実施に関する実態調査－TDM実施率と感染制御体制との関連性およびTDMの実施方法の抗菌薬TDMガイドラインとの比較－.

松元一明, 磯田梨奈, 黒田裕子, 横山雄太, 木津純子.

日本化学療法学会雑誌 65   175 - 182 2017年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1340-7007

Synthesis of linezolid metabolites PNU-142586 and PNU-142300 toward the exploration of metabolite-related events.

Kengo Hanaya, Kazuaki Matsumoto, Yuta Yokoyama, Junko Kizu, Mitsuru Shoji, Takeshi Sugai.

CHEMICAL & PHARMACEUTICAL BULLETIN 65   194 - 199 2017年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1347-5223

有害事象自発報告データベース（JADER）からみた医薬品による交通事故.

安藤剛, 松元一明, 横山雄太, 木津純子.

日本交通科学協議会誌 16   46 - 51 2017年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  13469282

CYP2C19遺伝子多型と代謝物濃度をふまえたTDMによるボリコナゾール投与量適正化が有用であった2例.

茂見茜里, 松元一明, 渡辺英里香, 猪川和朗, 金澤直子, 横山雄太, 梅﨑雄太, 池田龍二, 森川則文, 武田泰生.

日本外科感染症学会雑誌 13   661 - 667 2016年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1349-5755

Pregabalin prescription for terminally ill cancer patients receiving specialist palliative care in an acute hospital.

Ryo Yajima, Kazuaki Matsumoto, Yuya Ise, Norihito Suzuki, Yuta Yokoyama, Junko Kizu, Shiro Katayama.

JOURNAL OF PHARMACEUTICAL HEALTH CARE AND SCIENCES 2   29 2016年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2055-0294

Pharmaceutical studies on and clinical application of olanzapine suppositories prepared as a hospital preparation.

Kazuaki Matsumoto, Satoru Kimura, Kenichi Takahashi, Yuta Yokoyama, Masayuki Miyazawa, Satoko Kushibiki, Morio Katamachi, Junko Kizu

JOURNAL OF PHARMACEUTICAL HEALTH CARE AND SCIENCES 2   20 2016年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2055-0294