著者

上井 優一 鈴木 里彩 岩本 喜久生

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.5, pp.853-861, 2011-05-01 (Released:2011-05-01)

参考文献数

28

被引用文献数

6 7

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It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) affect the pharmacokinetics of methotrexate, but there are several reports showing negative consequences. In this study, we evaluated drug interactions by performing a meta-analysis on published data examining the effect of NSAIDs on pharmacokinetic parameters of methotrexate. The combined standardized mean difference of the maximum blood concentration after oral administration of methotrexate was calculated to be −0.00 (95% confidence interval, −0.30 to 0.30) based on 6 clinical trials, and there was no significant effect of NSAIDs (p=0.9967). However, it is also represented that the NSAIDs significantly increased the area under the blood concentration-time curve of methotrexate (combined standardized mean difference, 0.73; 95% confidence interval, 0.32 to 1.14; p=0.0004; 11 trials). Furthermore, the combined standardized mean differences in total and renal clearance of methotrexate were estimated to be −0.80 (95% confidence interval, −1.41 to −0.18; p=0.0109; 6 trials) and −0.76 (95% confidence interval, −1.40 to −0.11; p=0.0220; 11 trials), respectively, implying that NSAIDs interfere with urinary excretion of methotrexate. In conclusion, the integration of the published reports by these meta-analyses shows that NSAIDs increase blood levels of methotrexate by influencing renal excretion of the antifolate.

著者

西村 信弘 土井 教雄 上村 智哉 竹谷 健 林 丈二 葛西 武司 金井 理恵 山口 清次 岩本 喜久生 直良 浩司

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.129, no.6, pp.759-766, 2009 (Released:2009-06-01)

参考文献数

21

被引用文献数

4 5

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A traditional Chinese herbal medicine, Kampo medicine, maoto, has been widely used in the treatment of febrile symptoms caused by viral infection. This herbal extract granule for oral use, however, is not well accepted by infants or young children due to its unpleasant taste and odor. Therefore, we prepared Kampo medicine, maoto, suppository and investigated the pharmaceutical and clinical efficacy of the suppository. Kampo medicine, maoto, granules were micro-pulverized and homogeneously dispersed into Hosco-H15 to prepare suppositories containing 0.25 to 1.0 g herbal extract by the conventional fusion method. Content of l-ephedrine, an index compound of Kampo medicine, maoto, in the extract granules and suppositories was determined by using a high performance liquid chromatographic method. Physicochemical experiments revealed that the suppository containing 0.5 g herbal extract had the most suitable melting point of 34°C. Contents of l-ephedrine in the suppository were constant, 93-96% of those in the same amount of the extract granules in different three lots. Upper and lower portions of the suppository had the same content of l-ephedrine. The suppository maintained more than 95% of l-ephedrine content through 6 months at 4°C, room temperature and 40°C, although maldistribution of the extract constituent was observed after storage at 40°C. The suppository was administered to 21 pediatric febrile patients at a dose of 1/3 to 2 full pieces depending on their body weight and physical status. Significant reduction (p<0.001) of body temperature from 39.5 to 37.5°C without serious adverse effects was observed in 17 patients who were monitored the clinical effects on the febrile symptoms. In conclusion, Kampo medicine, maoto, suppository was found to satisfy the physicochemical quality and quantity standards as well as to be clinically applicable to neonates, infants and children with viral febrile symptoms without any adverse effects.