Murakami M, Miyachi Y, Nanno M, Yoshimi T
2nd Department of Internal Medicine, Hamamatsu University School of Medicine.
Nihon Naibunpi Gakkai Zasshi. 1990 Aug 20;66(8):760-9. doi: 10.1507/endocrine1927.66.8_760.
Dexamethasone (DXM), one of the strong synthetic glucocorticoids, has been used widely for therapeutic purposes and for evaluation of the hypothalamic-pituitary-adrenal axis. However, information concerning the plasma concentrations of DXM and its metabolism in various liver diseases is limited. In this study, plasma DXM levels were examined in patients with chronic inactive hepatitis (CH), patients with liver cirrhosis (LC) and normal subjects (NR) after oral administration of one milligram DXM. Plasma DXM levels were measured directly in plasma extract, using reliable and sensitive radioimmunoassay (RIA). The antiserum was obtained by immunizing rabbits with DXM-3-oxime-bovine serum albumin conjugate. Standard curves for DXM were obtained over the range 10-5000 pg. The cross reactivity of endogenous steroids with DXM antiserum was less than 0.1%. In the group of NR, the peak of plasma DXM was 20.9 +/- 2.9 ng/ml within 1.3 +/- 0.4 hours after administration. Half time of its disappearance was 3.3 +/- 1.1 hours, and plasma DXM disappeared in 24 hours, remaining less than 1 ng/ml. In patients with CH and those with LC, the peak levels of DXM were 10.8 +/- 1.0 ng/ml and 10.5 +/- 0.5 ng/ml, respectively, and those values were significantly lower than those of NR. Half time of DXM disappearance in patients with CH and in those with LC were 6.2 +/- 0.6 and 6.3 +/- 0.6 hours, respectively, significantly prolonged compared with that of NR. Although DXM metabolism was impaired in CH as well as in LC, the retention rate of indocyanine green (ICG) at 15 minutes in CH was found within the normal range, 10.0 +/- 1.1%, respectively. These results might suggest that the impaired DXM metabolism in patients with chronic liver disease may be affected not only by the decreased hepatic blood flow but also by some other factors.
地塞米松（DXM）是一种强效合成糖皮质激素，已被广泛用于治疗目的以及评估下丘脑 - 垂体 - 肾上腺轴。然而，关于DXM在各种肝脏疾病中的血浆浓度及其代谢的信息有限。在本研究中，对慢性非活动性肝炎（CH）患者、肝硬化（LC）患者和正常受试者（NR）口服1毫克DXM后检测其血浆DXM水平。使用可靠且灵敏的放射免疫分析（RIA）直接在血浆提取物中测量血浆DXM水平。通过用DXM - 3 - 肟 - 牛血清白蛋白结合物免疫兔子获得抗血清。DXM的标准曲线在10 - 5000 pg范围内获得。内源性类固醇与DXM抗血清的交叉反应性小于0.1％。在NR组中，给药后1.3±0.4小时内血浆DXM峰值为20.9±2.9 ng/ml。其消失半衰期为3.3±1.1小时，血浆DXM在24小时内消失，残留量低于1 ng/ml。在CH患者和LC患者中，DXM的峰值水平分别为10.8±1.0 ng/ml和10.5±0.5 ng/ml，这些值明显低于NR组。CH患者和LC患者中DXM消失的半衰期分别为6.2±0.6小时和6.3±0.6小时，与NR组相比显著延长。虽然CH和LC患者的DXM代谢均受损，但CH患者15分钟时吲哚菁绿（ICG）潴留率在正常范围内，分别为10.0±1.1％。这些结果可能表明，慢性肝病患者DXM代谢受损可能不仅受肝血流量减少的影响，还受其他一些因素的影响。
