著者

佐井 君江 澤田 純一 南 博信

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.128, no.4, pp.575-584, 2008 (Released:2008-04-01)

参考文献数

42

被引用文献数

10 19

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Recent progress in pharmacogenetic research has made “personalized medicine” a reality, where a suitable drug at the appropriate dosage is prescribed based on individual genetic factors. Irinotecan, an anticancer drug, is one of the models for personalized medicine, and a number of clinical studies have revealed significant associations between UGT1A1*28 and irinotecan toxicity. Based on the cumulative evidence, clinical tests for the UGT1A1*28 marker have started in the United States since 2005. However, the appropriate criteria for irinotecan dose adjustments have not yet been fully established. Since there are considerable differences in genetic polymorphisms among different ethnic groups and in approved irinotecan-containing regimens between countries, the criteria for the choice of suitable genetic markers and dose adjustments should be standardized in each country. This mini-review outlines our recent studies on irinotecan pharmacogenetics and discusses the clinical significance of UGT1A1*6 and *28 markers for personalized irinotecan therapy in Japanese cancer patients.

著者

林 恭子 大津 史子 矢野 玲子 榊原 仁作 後藤 伸之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.131, no.1, pp.139-152, 2011 (Released:2011-01-01)

参考文献数

32

被引用文献数

3 3

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The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting.

著者

菅谷 幸子 吉葉 孝子 梶間 隆 石濱 泰

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.122, no.3, pp.237-246, 2002 (Released:2003-02-18)

参考文献数

15

被引用文献数

12 21

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We developed two methods for solubility screening of drug candidates in drug discovery. The first is a solution-precipitation (SP) method, in which the sample solutions are prepared by adding the drug solution in dimethylsulfoxide (DMSO) to buffers followed by filtering off the precipitate using 96-well filterplate. The second is a powder-dissolution (PD) method, in which the solid samples are dissolved to the buffer in the HPLC vial equipped with the filter membrane in the HPLC autosampler. An HPLC equipped with a photodiode array detector is used to measure the concentration of the sample solutions in both methods. The SP method was used for high throughput screening the solvating process of the candidates in aqueous solutions with lower sample consumption, and the PD method was used for screening both inter-molecular interaction in solid state and solvation in aqueous solution with more sample amount than that of SP method. Therefore, the solubility screening from early to final stage of lead optimization process would be successfully accomplished by using both methods complementarily.

著者

潮平 英郎 仲松 正司 喜瀬 勇也 比嘉 太 健山 正男 外間 惟夫 国吉 幸男 植田 真一郎 中村 克徳 藤田 次郎

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.9, pp.1313-1317, 2016 (Released:2016-09-01)

参考文献数

16

被引用文献数

1 2

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Teicoplanin, a glycopeptide antibiotic for methicillin-resistant Staphylococcus aureus, is recommended for therapeutic drug monitoring during treatment. Maintaining a high trough range of teicoplanin is also recommended for severe infectious disease. However, the optimal dose and interval of treatment for severe renal impairment is unknown. We report a 79-year-old man who received long-term teicoplanin treatment for methicillin-resistant Staphylococcus aureus bacteremia due to postoperative sternal osteomyelitis with renal impairment. Plasma teicoplanin trough levels were maintained at a high range (20-30 μg/mL). Although the patient required long-term teicoplanin treatment, a further decline in renal function was not observed, and blood culture remained negative after the start of treatment. Teicoplanin treatment that is maintained at a high trough level by therapeutic drug monitoring might be beneficial for severe methicillin-resistant Staphylococcus aureus infection accompanied by renal impairment.

著者

香川 靖雄

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.107, no.11, pp.835-848, 1987-11-25 (Released:2008-05-30)

参考文献数

38

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Adenosinetriphosphate (ATP) synthase (FoF1) is a major energy supplying enzyme of cells utilizing the proton motive force. It consists of a catalytic portion called F1 and a proton channel portion called Fo. In order to elucidate the chemical reaction of FoF1, thermophilic FoF1 (TFoF1) was used, because it is stable and could eb reconstituted without Mg-ATP. In contrast to the previous hypotheses on the ATP synthesis, direct measurement of H+ current through TFoF1 incorporated into a planar lipid bilayer, 3H+/ATP stoichiometry was obtained. The primary structure of TFoF1 was established by sequencing its operon deoxyribonucleic acid and subunit peptides. The stereochemistry of the reaction using [16O, 17O, 15O, 35S] thiophosphate supported the a pathway for associative nucleophilic displacement on a phosphoric ester without pseudorotation. The diastereoisomeric preference of Cd-ATPγS revealed that the true substrate of TFoF1 is Δ, β, γ, bidentate Mg-ATP, like adenylate kinase. The site directed mutagenesis of the residues of F1 homologous to Mg-ATP binding site of adenylate kinase revealed their essential role in the reaction. Mitchell's chemiosmotic theory was refined by these results.

著者

朝比奈

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

no.319, pp.934-935, 1908-09-26

著者

畝山 寿之 竹内 孝治

出版者

公益社団法人日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.131, no.12, pp.1675-1676, 2011 (Released:2011-12-01)

参考文献数

8

著者

岡崎 研太郎

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.3, pp.351-355, 2015 (Released:2015-03-01)

参考文献数

8

---

The empowerment approach to patients with diabetes is a philosophy that was introduced by Robert M. Anderson and Martha M. Funnell of Michigan Diabetes Research and Training Center in the 1990s. This approach is based on the observation that more than 98% of diabetes care is performed by patients themselves. Dr. Anderson, Ms. Funnell, and their colleagues found that every patient has a right and an ability to solve his/her own problem in his/her own diabetes. Therefore healthcare providers should provide support for patients own endeavors. Empowerment has three essential elements: 1) the patient is centered, they make a final decision of their daily self-management, and are responsible for those decisions and the results; 2) patient support is the main role of healthcare providers; and 3) patient and healthcare providers should collaborate. In this author's opinion, it is important for healthcare providers to improve their communication skills to use the empowerment approach to help patients change their behaviors in the real world. To encourage empowerment, we created a unique learning program for healthcare providers, named “Diabetes Theater”. This program is an interactive workshop comprising two parts: drama and discussion.

著者

佐々木 俊則 大島 有美子 三島 江津子 伴 晶子 桂川 健司 永松 秀紹 吉岡 祐貴 築山 郁人 久田 達也 板倉 由縁 水谷 三浩

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.7, pp.1023-1029, 2016 (Released:2016-07-01)

参考文献数

15

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It is often necessary to modify the dose or schedule of eribulin mesilate (Eri) because of adverse events. Therefore, we retrospectively investigated the optimal approach for Eri dose adjustment and/or dosage interval adjustment. Patients who received Eri at the institutions affiliated with the Division of Oncology of the Aichi Prefectural Society of Hospital Pharmacists between July 2011 and November 2013 were enrolled in this study. We compared the group that underwent dose reduction without changes to their dosage interval (dose reduction group) with the group that had a change in their dosage interval (dose-interval prolongation group). The primary end-point was time to treatment failure (TTF), and the secondary end-points were overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and adverse events. The TTF and OS of the dose reduction group were approximately two times longer than those of the dose-interval prolongation group. In addition, the dose reduction group had significantly improved ORR and CBR, which together indicate an antitumor effect (p=0.013 and 0.002, respectively). Although peripheral neuropathy occurred significantly more frequently in the patients in the dose reduction group (p=0.026), it was grade 1 and controllable in most of the cases. There were no differences in the occurrence of other adverse effects between the two groups. Therefore, we suggest that dose reduction with maintenance of the dosage interval is the preferred treatment approach in cases where Eri dose or schedule modification is necessary.

著者

座間味 義人 小山 敏広 今井 徹 武本 あかね 相良 英憲 千堂 年昭 名倉 弘哲

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.7, pp.987-991, 2016 (Released:2016-07-01)

参考文献数

6

被引用文献数

2

---

Pharmacists are expected to be active members of the healthcare team in emergency medicine, because many pharmaceuticals are administered to patients with life-threatening conditions. However, adequate education for pharmacists and pharmacy students is not provided. The “Emergency Pharmaceutical Sciences” course was introduced for the first time in Japan by the Department of Pharmacy, Okayama University, to offer advanced education in emergency medicine and research related to critical care. We offer an emergency pharmaceutical training program with high-performance simulators and have succeeded in improving the clinical skills and confidence of pharmacy students. In this review, we introduce our activities intended to mold pharmacy students into emergency pharmacists who can contribute to emergency medicine.

著者

座間味 義人 小山 敏広 名倉 弘哲 榎本 秀一

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.7, pp.965-965, 2016 (Released:2016-07-01)

著者

喜谷 喜徳

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.105, no.10, pp.909-925, 1985-10-25 (Released:2008-05-30)

参考文献数

46

被引用文献数

1 2

---

Since the discovery of antitumor activity of cis-Platin by Rosenberg in 1969, various Pt complexes were prepared in order to ameliolate severe kidney toxicity, and vomiting and nausea. Pt complexes have usually high antitumor activity against leukemia L1210. Various antitumor Pt complexes were prepared, with an aim to synthesize the 2nd generation Pt complexes with high and specific antitumor activity without or least toxicity. Various Pt complexes of 1, 2-cyclohexanediamine (dach) and 2-(aminomethyl)-cyclohexylamine (amcha) isomers were prepared as carrier ligands, and mono- and bi-dentate leaving groups. Among the carrier ligands, trans-l-dach, and cis-dl- and trans-dl-amcha are found to be the most antitumor active ligands with 5-membered and 6-membered chelate rings. Water-soluble Pt complexes and lipo-soluble Pt complexes were also prepared by the modification of leaving groups. They are highly antitumor active. Among the Pt complexes prepared so far, Pt (oxalato) (trans-l-dach), as well as Pt (D-glucuronato) (trans-l-dach) nitrate and Pt (D-glucuronato)2 (trans-l-dach) are under development as a new type of the antitumor agent. The interactions of Pt complexes with deoxyribonucleic acid (DNA) were discussed. The mode of action of Pt complexes has been found to be mainly intrastrand crosslinking at N7 of guanine base. The measurements were carried out by the exonuclease enzyme digestion of Pt-DNA complexes, followed by the detection with high performance liquid chromatography. Pt (oxalato) (trans-l-dach) is recommended as the promising 2nd generation Pt complex.

著者

王 誠明 太田 節子 篠田 雅人

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.109, no.12, pp.949-953, 1989-12-25 (Released:2008-05-30)

参考文献数

24

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The survival effect of mice irradiated with a lethal dose of X-ray was studied by use of 60 kinds of Chinese traditional medicines. Methanol extracts of these medicines were prepared, and then each extract injected intraperitoneally into male mice before or after whole-body irradiation. As a result of these studies, the survival effects with Ogi-kentyu-to, Simotu-to, Sessyoin, Zokumei-to and Boi-ogi-to were observed by intraperitoneal injection before irradiation. Of these effective methanol extracts, only Zokumei-to was shown to have a significant survival effect by intraperitoneal injection after irradiation.

著者

中山 祥嗣

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.6, pp.795-798, 2016 (Released:2016-06-01)

参考文献数

1

被引用文献数

1

---

The Japan Ministry of the Environment is conducting a large-scale birth cohort study called the Japan Environment and Children's Study (JECS), which involves 100000 mother-child pairs. Mothers are enrolled during pregnancy, and their children are followed up and studied until they reach the age of 13 years. The JECS started recruiting mothers in January 2011 and completed the registration of more than 103000 mothers in March 2014. The National Institute for Environmental Studies takes the lead in the study programming and implementation in cooperation with the National Centre for Child Health and Development and 15 Regional Centres that reach out to the study participants. In the study, the effects of environmental factors on children's health and development are investigated. The environment in this study is defined not only as air, soil, water, and indoor environments but also as various chemical substances, physical conditions, socioeconomic factors, psychological conditions, lifestyles and community situations. Mothers' and children's exposures to these environmental factors are measured through chemical analyses of biospecimens collected during pregnancy and after birth, questionnaires and computer modelling. The homes of the randomly selected participants (5000) are visited to measure the concentrations of volatile organic compounds, nitrogen and sulphuric oxides and particulate matter. Vacuum dust samples are also collected for chemical analysis. All these data will be combined with the information collected by the dwelling unit observation to assess the exposure of children aged 1.5 and 3 years.

著者

高田 善之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.80, no.11, pp.1640-1641, 1960-11-25 (Released:2010-02-19)

参考文献数

3

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Application of alkaline hydrogen peroxide to sodium 2-cyanoethanesulfonate, obtained by reaction of acrylonitrile and sodium hydrogensulfite, afforded sodium 2-carbamoylethanesulfonate. Taurine (2-aminoethanesulfonic acid) was obtained in a comparatively good yield of 80-85% by reaction of the foregoing sulfonate and alkaline sodium hypochlorite.

著者

藤田 直

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.122, no.3, pp.203-218, 2002 (Released:2003-02-18)

参考文献数

60

被引用文献数

21 40

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It is well known that biomembranes and subcellular organelles are susceptible to lipid peroxidation. There is a steadily increasing body of evidence indicating that lipid peroxidation is involved in basic deteriorative mechanisms, e.g., membrane damage, enzyme damage, and nucleic acid mutagenicity. The formation of lipid peroxides can be induced by enzymatic or nonenzymatic peroxidation in the presence of oxygen. The mechanisms of formation and removal of reactive oxygen species, lipid peroxides, and free radicals in biological systems are briefly reviewed. In recent years, there has been renewed interest in the role played by lipid peroxidation in many disease states. Xanthine oxidase has been shown to generate reactive oxygen species, superoxide (O2−·), and hydrogen peroxide (H2O2) that are involved in the peroxidative damage to cells that occurs in ischemia-reperfusion injury. During ischemia, this enzyme is induced from xanthine dehydrogenase. We have shown that peroxynitrite (a reactive nitrogen species) has the potential to convert xanthine dehydrogenase to oxidase. The following biological effects of lipid peroxidation were found: a) the lipid peroxidation induced by ascorbic acid and Fe2+ affects the membrane transport in the kidney cortex and the cyclooxygenase activity in the kidney medulla, and b) the hydroperoxy adducts of linoleic acid and eicosapentaenoic acid inhibit the cyclooxygenase activity in platelets. The balance between the formation and removal of lipid peroxides determines the peroxide level in cells. This balance can be disturbed if cellular defenses are decreased or if there is a significant increase in peroxidative reactions. Once lipid peroxidation is initiated, the reactive intermediate formed induces cell damage.

著者

石黒 正路 西原 達郎 田中 里枝

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.121, no.12, pp.915-927, 2001-12-01 (Released:2002-09-27)

参考文献数

33

被引用文献数

5 8

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An orally active penem antibiotic, Farom (generic name: faropenem), was designed by the conformational analysis of active and inactive penem derivatives. Faropenem showed potent activity against a wide variety of bacteria including extended-spectrum β-lactamase (ESBL)-producing ones. The mechanism of the stability against ESBL was elucidated by modeling the Michaelis complex of faropenem and Toho-1, an ESBL. Modeling of a complex of faropenem at the active site of a penicillin-binding protein 2 (PBP2) model suggested the characteristic affinity for faropenem with PBP2 of Escherichia coli. Faropenem has been totally synthesized from (R)-1,3-butanediol. The synthetic intermediate, a 3-hydroxyethyl-4-acetoxyazetidinone derivative, was efficiently prepared by the 2+2 coupling of a optically active vinyl-sulfide derivative and chlorosulfonyl isocyanate, followed by the substitution of the acetoxy group for the thiophenyl group at the C-4 position.

著者

小松 生明

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.2, pp.329-335, 2016-02-01 (Released:2016-02-01)

参考文献数

34

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Morphine with its potent analgesic property has been widely used for the treatment of various types of pain. However, the intrathecal (i.t.) administration of morphine at doses far higher than those required for antinociception exhibited nociceptive-related behaviors consisting of scratching, biting and licking, hyperalgesia, and allodynia in mice. Morphine-3-glucuronide (M3G), one of the major metabolites of morphine, has been found to evoke nociceptive behaviors similar to those after high-dose i.t. morphine. It is plausible that M3G may be responsible for nociception seen after high-dose i.t. morphine treatment. This article reviews the potential mechanism of spinally mediated nociceptive behaviors evoked by i.t. M3G in mice. We discuss the possible presynaptic release of nociceptive neurotransmitters/neuromodulators such as substance P, glutamate, dynorphin, and Leu-enkephalin in the primary afferent fibers following i.t. M3G administration. It is possible to speculate that i.t. M3G could indirectly activate NK1, NMDA, and δ2-opioid receptors that lead to the release of nitric oxide (NO) in the dorsal spinal cord. The major function of NO is the production of cGMP and the activation of protein kinase G (PKG). The NO-cGMP-PKG pathway plays an important role in M3G-induced nociceptive behavior. The phosphorylation of extracellular signal-related kinase (ERK) in the dorsal spinal cord was also evoked via the NO-cGMP-PKG pathway through the activation of δ2-opioid, NK1, and NMDA receptors, contributing to M3G-induced nociceptive behaviors. The demonstration of a neural mechanism underlying M3G-induced nociception provides a pharmacological basis for improved pain management with morphine at high doses.

著者

野口 照久 橋本 喜信 小坂 璋吾 菊池 正義 宮崎 幸信 先本 礼次 加治 有恒

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.88, no.3, pp.344-352, 1968-03-25 (Released:2008-05-30)

参考文献数

21

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Some observations were made on the anti-trichophyton action of 2-naphthyl N-methyl-N-arylthiocarbamate (A). In vitro antifungal activity decreased slightly when the thiocarbamate was changed to carbamate, and a marked lowering in the in vitro effect was observed. The antifungal activity disappeared entirely when the thiocarbamate was changed to dithiocarbamate and thiolcarbamate. When the aryl group in A is a naphthyl, antifungal activity is present only when 1-naphthyl is present and other three combinations are entirely ineffective. When the aryl is a substituted phenyl, compounds having methyl, methoxyl, or halogens, those with the Hammet constant in the range of +0.23 to -0.27, have marked antitrichophyton activity in vivo, but those with nitro, formyl, carboxyl, sulfonamido hydroxyl, or dimethylamino group show marked decrease in the effect. The series of compounds having the A type will henceforth be designated as naphthiomates.

著者

野口 照久 小坂 璋吾 橋本 喜信 菊池 正義 宮崎 幸信 加治 有恒

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.88, no.3, pp.353-358, 1968-03-25 (Released:2008-05-30)

参考文献数

16

被引用文献数

1 2

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Examinations were made on the effect of oral administration of 2-naphthyl N-methyl-N-arylthiocarbamates (naphthiomates), an effective antimicotic agent for external use, against experimental trichophytosis. Finely powdered 2-naphthyl N-methyl-N-(m-tolyl)-thiocarbamate (naphthiomate-T) and 2-naphthyl N-methyl-N-(1-naphthyl) thiocarbamate (naphthiomate-N) showed an effect comparable to griseofulvin in about four-fold dose of the latter. In vivo metabolism of naphthiomate-T was examined in guinea pigs and rabbits, and it was found that the majority is excreted in the feces without decomposition, and little is absorbed through the intestinal tract. N-Methyl-m-toluidine and β-naphthol were detected from urine, feces, and blood as the metabolites.