Radioimmunoassay for Dexamethasone and its Plasma Levels After Oral Administration in Patients with Liver Disease

Abstract

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.