Kawai S
Nihon Naibunpi Gakkai Zasshi. 1985 Mar 20;61(3):145-61. doi: 10.1507/endocrine1927.61.3_145.
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 1 mg 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 (t 1/2), metabolic clearance rates (MCR) and total apparent distribution volumes (V) of these glucocorticoids were calculated using the single compartment model. The mean values of t 1/2 of cortisol, prednisolone and dexamethasone in patients with collagen diseases under RFP therapy were 1.8 +/- 0.3 (Mean +/- SD) (p less than 0.05), 1.4 +/- 0.2 (p less than 0.001) and 1.3 +/- 0.3 hours (p less than 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 less than 0.01) and 722 +/- 137 l/day/m2 (p less than 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 t 1/2 of cortisol, prednisolone and dexamethasone in patients with tuberculosis alone under RFP therapy were 1.3 +/- 0.3 (p less than 0.001), 1.4 +/- 0.5 (p less than 0.01) and 1.2 +/- 0.3 hours (p less than 0.001), respectively, which were significantly shortened when compared with normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
尽管利福平（RFP）是已知的强效肝微粒体酶诱导剂之一，但关于接受RFP治疗的患者中糖皮质激素详细的药代动力学情况，此前报道甚少。本文通过同时注射这些糖皮质激素，对皮质醇、泼尼松龙和地塞米松的代谢进行了比较研究。研究对象为11例接受RFP治疗的患者，其中7例患有结核病合并胶原病，4例仅患有结核病。还检测了16名正常志愿者和4例未接受RFP治疗的胶原病患者作为对照。在前一晚口服1mg倍他米松以抑制内源性皮质醇后，静脉注射分别含1mg皮质醇、泼尼松龙和地塞米松的混合溶液。定期采集血样，经二氯甲烷萃取并用纸色谱法纯化后，通过各自的放射免疫分析法测定血浆类固醇水平。使用单室模型计算这些糖皮质激素的血浆消除半衰期（t 1/2）、代谢清除率（MCR）和总表观分布容积（V）。接受RFP治疗的胶原病患者中，皮质醇、泼尼松龙和地塞米松的t 1/2平均值分别为1.8±0.3（平均值±标准差）（p<0.05）、1.4±0.2（p<0.001）和1.3±0.3小时（p<0.001），与正常受试者相比（皮质醇，2.1±0.2；泼尼松龙，2.5±0.7；地塞米松，3.5±1.0小时）显著缩短。这些患者中皮质醇、泼尼松龙和地塞米松的MCR分别为139±57、141±53（p<0.01）和722±137 l/天/m2（p<0.001），与正常受试者相比（皮质醇，114±20；泼尼松龙，75±25；地塞米松，153±45 l/天/m2）升高。与未接受RFP治疗的胶原病患者相比，接受RFP治疗的胶原病患者中这些糖皮质激素的代谢也加快。仅患有结核病且接受RFP治疗的患者中，皮质醇、泼尼松龙和地塞米松的t 1/2分别为1.3±0.3（p<0.001）、1.4±0.5（p<0.01）和1.2±0.3小时（p<0.001），与正常受试者相比显著缩短。（摘要截选至400字）
