title: Development and testing in healthy adults of oral hydrocortisone granules with taste masking for the treatment of neonates and infants with adrenal insufficiency.
abstract: BACKGROUND
  Treatment of neonates and infants with adrenal insufficiency is unsatisfactory because unlicensed hydrocortisone formulations are used.
  
  
  OBJECTIVE
  The objectives were to survey current hydrocortisone prescribing practice and develop a novel hydrocortisone formulation, Infacort.
  
  
  METHODS
  The use of hydrocortisone by European pediatric endocrinologists was surveyed. Based on this, an oral hydrocortisone granule formulation, Infacort, with taste masking was developed and evaluated in vitro and then in vivo in a phase I pharmacokinetic study.
  
  
  RESULTS
  The survey showed that pediatricians use a variety of unlicensed compounded adult medications at doses of between 0.5 and 5 mg. Infacort was formulated with a taste-masking layer stable for at least 5 minutes in aqueous media and was produced in unit doses of 0.5, 1, 2, and 5 mg. Infacort 10 mg is the bioequivalent of a 10-mg hydrocortisone tablet (mean area under the curve from zero to infinity [AUC(0-inf)] ratio, 101%; 90% confidence interval, 96-107%). Mean cortisol maximum concentration (C(max)) and AUC(0-inf) values after administration of Infacort were linear with dose and dose proportional when adjusted for saturable plasma protein binding. Subjects rated Infacort as "not good or bad" for smell (86%), feel in the mouth (71%), and taste (79%). No serious adverse events were reported.
  
  
  CONCLUSIONS
  This phase 1 study demonstrates that Infacort is safe, well tolerated, of neutral taste, bioequivalent to hydrocortisone licensed for adults, and shows dose proportionality with respect to cortisol exposure. Infacort is expected to facilitate optimization of hydrocortisone dosing in neonates and children with adrenal insufficiency; however, clinical studies will be required to demonstrate efficacy in this patient age group.
authors: The University of Sheffield (M.J.W., G.T., R.J.R.), Sheffield S10 2TN, United Kingdom; Diurnal Limited (D.D., H.H., D.E.), Cardiff CF14 4UJ, United Kingdom; Charité Universitätsmedizen (S.S., H.K., O.B.), 13353 Berlin, Germany; and Simcyp (Certara) Ltd (T.N.J., G.T.), Sheffield S2 4SU, United Kingdom.
authors: Martin J
authors: MJ
authors: Whitaker
authors: Sarah
authors: S
authors: Spielmann
authors: Dena
authors: D
authors: Digweed
authors: Hiep
authors: H
authors: Huatan
authors: David
authors: D
authors: Eckland
authors: Trevor N
authors: TN
authors: Johnson
authors: Geoffrey
authors: G
authors: Tucker
authors: Heiko
authors: H
authors: Krude
authors: Oliver
authors: O
authors: Blankenstein
authors: Richard J
authors: RJ
authors: Ross
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000309:Adrenal Insufficiency / Q000151:congenital* / Q000188:drug therapy; D000328:Adult; D018592:Cross-Over Studies; D004304:Dosage Forms; D064368:Healthy Volunteers; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010159:Palate; D013649:Taste / Q000187:drug effects; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D004304:Dosage Forms; D006854:Hydrocortisone