Hydrocortisone Granules Are Bioequivalent When Sprinkled Onto Food or Given Directly on the Tongue

Abstract

Background

Immediate-release hydrocortisone granules in capsules for opening in pediatric-appropriate doses have recently been licensed for children with adrenal insufficiency. This study evaluated the bioavailability of hydrocortisone granules administered as sprinkles onto soft food and yogurt compared with direct administration to the back of the tongue.

Methods

Randomized, 3-period crossover study in 18 dexamethasone-suppressed healthy men. In each period, the fasted participants received 5 mg hydrocortisone granules either directly to the back of the tongue or sprinkled onto soft food (applesauce), or yogurt, followed by 240 mL of water. Serum cortisol was measured by liquid chromatography tandem mass spectometry.

Results

The cortisol geometric mean maximum concentration (C _max) and area under the curve (AUC) for direct administration, sprinkles onto yogurt, and sprinkles onto soft food were: C _max 428, 426, 427 nmol/L and AUC _0-inf 859, 886, 844 h × nmol/L, and AUC _0-t 853, 882, 838 h × nmol/L respectively. The 90% CI for the ratios of C _max, AUC _0-inf and AUC _0-t for administration with soft food or yogurt to direct administration were well within the bioequivalent range, 80% to 125%. Median time to Cmax (T _max) was similar between methods of administration: 0.63 hours administered directly, 0.75 hours on soft food and 0.75 hours on yogurt. No adverse events occurred during the study.

Conclusions

Hydrocortisone granules administered as sprinkles onto soft food or yogurt but not mixed with these foods are bioequivalent to those administered directly to the back of the tongue. Carers, parents, or patients may choose to administer hydrocortisone granules either directly or sprinkled onto soft food or yogurt.