著者
川合 眞一
出版者
一般社団法人 日本内分泌学会
雑誌
日本内分泌学会雑誌 (ISSN:00290661)
巻号頁・発行日
vol.61, no.3, pp.145-161, 1985-03-20 (Released:2012-09-24)
参考文献数
47
被引用文献数
3 4

Although rifampicin (RFP) is known to be one of the potent hepatic microsomal enzyme inducers, little has been reported about the detailed pharmacokinetics of glucocorticoids in patients under RFP therapy. In this paper, the metabolism of cortisol, prednisolone and dexamethasone were investigated comparatively by simultaneous injection of these glucocorticoids.Eleven patients under RFP therapy, including 7 with tuberculosis together with collagen diseases and 4 with tuberculosis alone, were studied. Sixteen normal volunteers and 4 patients with collagen diseases not under RFP therapy were also examined as controls. After 1 mg of betamethasone was administered orally on the previous night for the suppression of endogenous cortisol, a mixed solution of 1mg each of cortisol, prednisolone and dexamethasone was given intravenously. Plasma steroid levels of periodically collected blood samples were determined by respective radioimmunoassay after extraction with dichloromethane and purification by paper chromatography.Half-times of plasma disappearance (t1/2), metabolic clearance rates (MCR) and total apparent distribution volumes (V) of these glucocorticoids were calculated using the single compartment model.The mean values of t1/2 of cortisol, prednisolone and dexamethasone in patients with collagen diseases under RFP therapy were 1.8±0.3 (Mean±SD) (p<0.05), 1.4±0.2 (p<0.001) and 1.3±0.3 hours (p<0.001), respectively, which were significantly shortened when compared with normal subjects (cortisol, 2.1±0.2; prednisolone, 2.5±0.7; dexamethasone, 3.5±1.0 hours). The MCR of cortisol, prednisolone and dexamethasone in these patients were 139±57,141±53 (p<0.01) and 722±137 l/day/m2 (p<0.001), respectively, which were increased when compared with normal subjects (cortisol, 114±20; prednisolone, 75±25; dexamethasone, 153±45 l/day/m2). The metabolism of these glucocorticoids in patients with collagen diseases under RFP therapy were also accelerated when compared with those in patients with collagen diseases not under RFP therapy.The t1/2 of cortisol, prednisolone and dexamethasone in patients with tuberculosis alone under RFP therapy were 1.3±0.3 (p<0.001), 1.4±0.5 (p<0.01) and 1.2±0.3 hours (p<0.001), respectively, which were significantly shortened when compared with normal subjects. The MCR of prednisolone and dexamethasone in these patients were significantly increased (136±72, p<0.05 and 868±226, p<0.001 l/day/m2) when compared with normal subjects.When these data were expressed as percent of mean values in normal subjects, the mean %-t1/2 of cortisol, prednisolone and dexamethasone were 86%, 56% and 37%, and the mean %-MCR were 122%, 188% and 472%, respectively, in patients with collagen diseases under RFP therapy. The mean %-t1/2 of these glucocorticoids in patients with tuberculosis alone under RFP therapy were 62%, 56% and 34%, and the mean %-MCR were 105%, 181% and 567%, respectively.The V of these glucocorticoids in patients under RFP therapy were almost the same as normal subjects except for that of dexamethasone, which was about twice as much as normal in patients both with or without collagen diseases.Five patients who were examined again after discontinuance of RFP showed normalization of this accelerated metabolism of prednisolone and dexamethasone.It may be concluded that marked differences in the degrees of accelerated metabolism between these glucocorticoids, the order of which was dexamethasone, prednisolone and cortisol, were observed in patients under RFP therapy. These results are very important in the concurrent use of glucocorticoid and RFP, especially when the tuberculosis therapy is needed in patients with collagen diseases under glucocorticoid therapy,
著者
川合 眞一
出版者
一般社団法人 日本内科学会
雑誌
日本内科学会雑誌 (ISSN:00215384)
巻号頁・発行日
vol.96, no.10, pp.2171-2176, 2007 (Released:2012-08-02)
参考文献数
6
被引用文献数
3 3

多発性筋炎(PM)/皮膚筋炎(DM)は,原因不明の炎症性ミオパチーであり,自己免疫疾患と考えられている.PMの診断は近位筋の筋力低下,血清筋原性酵素濃度の上昇,筋電図での筋原性変化,筋生検所見によるが,DMでは顔面などに特徴的皮疹を認める.筋外症状としては,急性間質性肺炎合併例の予後は悪い.治療は大量ステロイド療法が一般的だが,メトトレキサートなどの免疫抑制薬や大量免疫グロブリン療法も試みられる.
著者
川合 眞一
出版者
一般社団法人 日本内科学会
雑誌
日本内科学会雑誌 (ISSN:00215384)
巻号頁・発行日
vol.100, no.10, pp.2910-2917, 2011 (Released:2013-04-10)
参考文献数
10
被引用文献数
2 4

関節リウマチ治療は生物学的製剤の登場などもあり,臨床的寛解のみならず機能的・構造的寛解をも目指すことが可能となった.しかし,その目標は生物学的製剤のみで達成できるものではなく,低分子抗リウマチ薬による治療が不可欠といえる.サラゾスルファピリジンは世界で広く使用され,わが国でもメトトレキサートに次いで使用されている.ここでは,本薬の作用機序,臨床的有用性をまとめ,本剤の位置付けについても考察したい.
著者
金子 開知 川合 眞一
出版者
日本臨床免疫学会
雑誌
日本臨床免疫学会会誌 (ISSN:09114300)
巻号頁・発行日
vol.34, no.3, pp.138-148, 2011 (Released:2011-06-30)
参考文献数
54
被引用文献数
2 4

グルココルチコイド(ステロイド)誘発性骨粗鬆症(GIOP)の発症機序は,ステロイドの骨組織の局所に対する作用と,カルシウム代謝の変化による二次性副甲状腺機能亢進症や下垂体ホルモン分泌抑制を介した性ホルモン分泌の抑制などのステロイドが全身に作用を介した機序が考えられている.近年,骨組織への直接作用が特に骨形成への影響が注目されている.骨代謝マーカーにおいては,ステロイド投与早期より骨形成マーカーは低下する.一方で,骨吸収マーカーは増加傾向を示す.GIOPの治療に対して,各国でガイドラインが作成されているが,ビスホスホネート製剤はGIOPにおける骨折抑制効果が多くの臨床研究から明らかにされており治療の第一選択となっている.また,ヒト組み換え副甲状腺ホルモン剤であるテリパラチドは,GIOPにおける骨折のリスクが高い患者において使用を考慮すべき薬剤である.さらに,抗receptor activator for nuclear factor κB ligand抗体製剤であるデノスマブは閉経後骨粗鬆症においての有用性が報告されておりGIOPでの効果が今後期待される.
著者
川合 眞一
出版者
一般社団法人 日本臨床リウマチ学会
雑誌
臨床リウマチ (ISSN:09148760)
巻号頁・発行日
vol.24, no.1, pp.88-89, 2012-03-30 (Released:2015-12-30)
参考文献数
4
著者
川合 眞一
出版者
一般社団法人 日本内科学会
雑誌
日本内科学会雑誌 (ISSN:00215384)
巻号頁・発行日
vol.104, no.9, pp.1937-1943, 2015-09-10 (Released:2016-09-10)
参考文献数
10
被引用文献数
1