Endocrine Abstracts

Replacing glucocorticoids in patients with adrenal insufficiency is challenging, as endogenous cortisol levels rise before waking. Currently we use steroid replacement first thing in the morning. Administration of a delayed release preparation last thing at night, if reliable, could mimic the rise in cortisol that occurs before waking. Lodotra is a modified release prednisone that has a delay in the onset of action, and when given last thing at night, might cause a rise in levels before awakening. We investigated the reliability of Lodotra absorption and conversion in the liver to prednisolone. Single doses of either standard prednisolone or Lodotra 5 mg were administered in the morning. Samples for serum prednisolone were taken at intervals.

Results: Lodotra was absorbed with a 5-h delay in one volunteer (see figure), so that if the drug is taken at bedtime (11pm), a rise on prednisolone levels would start at 0400 h, consistent with the circadian rhythm.

Lodotra was not consistently absorbed in all three volunteers. Volunteers 2 and 3 showed negligible to low levels of prednisolone absorption for a 10 hour period. Food intake did not change absorption in any of the volunteers.

Conclusion: Because of its variable absorption, we cannot recommend the use of Lodotra for primary or secondary adrenal insufficiency.