麻豆传媒

CHICAGO -- Hydrocortisone granules were bioequivalent regardless of the method of administration, researchers reported here.

Infacort hydrocortisone granules sprinkled into food worked as well as granules administered dry to the back of the tongue, according to Eleni Daniel, MSc, MRCP, of the University of Sheffield in England, and colleagues.

Currently, there is no licensed pediatric hydrocortisone formulas that are dose-appropriate for infants and young children, Daniel said in a late-breaking presentation at ENDO 2018. Instead, current practice typically involves use of compounded hydrocortisone that is usually prepared by the child's caregiver or pharmacy.

Prior suggested roughly a quarter of compounded batches prepared by pharmacies, and around half prepared by the child's parents, are out of specification, with a high inaccuracy of the administered dose.

These findings are helpful for both parents and other caregivers of infants and children, where medication administration with food is common, according to Daniel.

"Infacort ...is a formulation of hydrocortisone granules in capsules for opening in doses of 0.5, 1.0, 2.0 and 5.0 mg with taste masking that has been shown to be well tolerated, easy to administer and to provide appropriate cortisol levels in neonates, infants and children," the authors wrote.

Daniel noted that Infacort was recently granted market authorization by the European Medicines Agency as replacement therapy for pediatric adrenal insufficiency. The granules does not have in the U.S.

"Previous treatment studies have shown that hydrocortisone granules are bioequivalent to tablets in adults and are well-absorbed in children," Daniel stated.

The three-period crossover study included 18 healthy adult males, who were dexamethasone-suppressed after fasting. They were administered 5 mg of immediate release Infacort hydrocortisone granules via one of three methods:

• Directly onto the back of the tongue with a spoon followed by water
• Sprinkled onto 5 mL applesauce
• Sprinkled onto 5 mL of yogurt

All methods achieved similar mean maximal serum cortisol concentration -- 428 nmol/L for direct, 426 nmol/L for yogurt, 427 nmol/L for soft food -- as was measured by liquid chromatography-mass spectrometry (LCMS-MS) pre-dose compared with up to 12 hours after the dose.

The group deemed all methods of administration bioequivalent, with similar mean areas under the curve (zero to infinity) -- 859, 886, 844 hours times nmol/L for direct, yogurt, and soft food methods, respectively.

Rate of absorption was also generally similar across the board with a median of rates of 38 minutes seen with use of dry granules and 45 minutes for both groups who received sprinkles on food.

Throughout the duration of the study, none of the three groups reported any adverse events with treatment.

"Carers, parents and patients may choose to administer hydrocortisone granules either directly as dry granules or sprinkled onto soft food or yogurt," Daniel stated, recommending "clinicians may advise that this is safe to do."

ENDO session co-chair Gail Kurr Adler, MD, PhD, of Brigham and Women's Hospital in Boston inquired as to whether children might respond differently than adults to this form of treatment.

Daniels replied that the dose can be titrated for pediatric patients. Also, because of the lower doses of hydrocortisone available in this formula, treatment can be optimized to improve both short-term and long-term outcomes, she said.

Comment