Pharmacokinetics of inhaled prednisolone for adrenal crisis: an exploratory study

An adrenal crisis is a potentially life-threatening medical emergency, which requires rapid treatment with glucocorticoids. Guidelines advise immediate self-administration of hydrocortisone by intramuscular injection using an emergency management kit in case an adrenal crisis is suspected. However, self-injection is often not performed due to administration complexity or patient anxiety. Pulmonary administration of glucocorticoids may be a more patient-friendly and suitable alternative, especially when administered using a dry powder inhaler. Before advancing to the development of a dry powder inhaler, we aimed to evaluate whether the pharmacokinetics of inhaled prednisolone sodium succinate are suitable for the outpatient treatment of adrenal crisis. Twelve healthy participants (aged 23-31 years, 50% females) received two separate doses of prednisolone sodium succinate, equivalent to 56.1 and 112.2 mg prednisolone on separate occasions, administered via a nebulizer. The primary outcome was the time to reach a target plasma concentration of 200 nmol/L. The median times to achieve this plasma concentration (excluding the nebulization time of approximately 10 minutes) were 17 (13 - 23) minutes and 9 (5-11) minutes for the 56.1 and 112.2 mg doses, respectively. Furthermore, pulmonary administered prednisolone sodium succinate was well tolerated. The results of this study, particularly the short time to the target plasma concentration, indicate that prednisolone sodium succinate is rapidly absorbed via the lungs and that the pharmacokinetics of inhaled nebulized prednisolone sodium succinate are suitable for the outpatient treatment of adrenal crisis.