BLOOD LEVELS OF SYNTHETIC GLUCOCORTICOIDS AFTER ADMINISTRATION BY VARIOUS ROUTES

Abstract

SUMMARY Using reliable radioimmunoassay methods, the concentrations of prednisolone, prednisolone-hemisuccinate, betamethasone and betamethasone-17-benzoate were determined after administration by various routes. Serum prednisolone and betamethasone concentrations increased to peak levels 2 h after oral administration and then decreased gradually. The half-times of disappearance of prednisolone and betamethasone from blood, after a single oral dose, were both approximately 180–220 min. Five to fifteen minutes after intramuscular injections of 20 mg prednisolone-hemisuccinate the peak serum concentration was 63·7 ± 7·4 μg/ 100 ml and 30 min later plasma unesterified prednisolone reached its highest level (28·8 ± 2·6 μg/100 ml). The administration of steroids through the rectum induced gradual increases in the levels of serum steroids, reaching a maximum of 25% of the peak serum concentrations observed after oral administration. Plasma betamethasone-17-benzoate levels of 300 ng/ 100 ml were observed after topical application of betamethasone-17-benzoate gel to the skin. In patients with liver disease, the clearance of betamethasone was very slow compared with that in normal control subjects and significant amounts were retained in the blood 24 h after oral administration, showing that the liver is the most important organ for the metabolism of synthetic glucocorticoid. The concentrations of prednisolone and prednisolone-hemisuccinate in the cerebrospinal fluid were very low after the intramuscular injection of prednisolone-hemisuccinate, confirming the relative impermeability of the blood–brain barrier to polar steroids.