- 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,