[Pharmacokinetics of prednisolone in adrenal insufficiency ]

Prednisolone was measured in serum and urine after oral and intravenous administration of prednisone and prednisolone in 16 patients with adrenal insufficiency and after bilateral adrenalectomy. Thus, the problem of cross-reactivity with endogenous steroids, the main factor disturbing the measurement of prednisolone, was completely eliminated. Prednisolone was detected by a simple competitive protein-binding radioassay. Distribution, elimination and other bioavailability parameters were calculated from the obtained data. No significant differences between serum levels were detected after oral administration of these drugs. Peak levels were reached after 2-3 h. After 5, 7.5 and 10 mg prednisone peak serum levels averaged 11.9 +/- 2.2, 15.9+/-3.4 and 21.5+/-5.9 microgram/dl, respectively. Prednisolone was still detectable 24 h after administration of 10 mg. The plasma half-time of approximately 5 1/2 h suggests that prednisolone is present in serum far about 2 days after application of higher doses. Since prednisolone interferes in most assays for cortisol, prednisone therapie has to be stopped at least 2 days before cortisol determinations. Urinary excretion was proportional to the applicated doses. The metabolic clearance rate of prednisolone was decreased (56.0+/-7.2 1/24 h/m2) in patients with adrenal insufficiency. This can be attributed to alterations in corticosteroid metabolism, probably due to an increased transcortin production.