Abstract
Hydrocortisone analogues have been used widely in therapy as a potent glucocorticoid, but very few studies of their plasma concentration, metabolism, properties of glucocorticoid receptor and biological effects have been published.
A sensitive and specific radioimmunoassay for betamethasone (BM) and prednisolone (P) has been developed 1, 2). Using this method plasma concentrations of BM and P were measured in normal subjects and patients with liver diseases following oral administration of BM and P. Plasma concentrations of BM were detected already at 20 min after administration in normal subjects. The peaks of the plasma concentrations were reached at 1 or 2 hours after administration but the wide variations of maximum values were observed in both normal subjects and patients with liver diseases. Peak levels of BM in patients with liver diseases were higher than those in normal subjects a little. After the peak levels plasma BM rapidly fell and disappeared at 24 hour post-administration in normal subjects. In patients with liver diseases the disappearances of BM from blood were markedly delayed and the relatively high plasma concentrations of BM were maintained even at 24 hour post-administration. The half-time of disappearance of BM from blood was 3 to 4 hours in normal subject. On the other hand it elongated to 5 to 6 hours in patients with liver diseases.
Plasma cortisol (Fk) levels were suppressed already at 20 min after administration of BM and rapidly fell in normal subjects, but the disapperance of Fk from blood markedly delayed in patients with liver diseases. The half-times of plasma Fk were 1 to 1.5 hours and more than 3 hours in normal subjects and patients with liver diseases respectively.
There was a good correlation between the severity of the liver disease as measured by the ICG retention at fifteen minutes and removals of BM and Fk from blood.
The peaks of the plasma concentrations of P were also reached at 1 or 2 hours after administration in normal subjects and patients with liver diseases, but peak levels of P in patients with liver diseases were lower than those in normal subjects. After the peak levels plasma P fell rapidly more than BM and disappeared at 24 hour post-administration in patients with liver diseaeses as well as in normal subjects. The half-time of disappearance of P from blood was 2.5 to 3 hours.
