title: Inhaled growth hormone (GH) compared with subcutaneous GH in children with GH deficiency: pharmacokinetics, pharmacodynamics, and safety.
abstract: BACKGROUND
  Delivery of GH via inhalation is a potential alternative to injection. Previous studies of inhaled GH in adults have demonstrated safety and tolerability.
  
  
  OBJECTIVE
  We sought to assess safety and tolerability of inhaled GH in children and to estimate relative bioavailability and biopotency between inhaled GH and sc GH.
  
  
  METHODS
  This pediatric multicenter, randomized, double-blind, placebo-controlled, crossover trial had two 7-d treatment phases. Patients received inhaled GH and sc GH in the alternate phase. Placebo was administered by the route opposite from active drug. GH and IGF-I levels were measured at multiple time points. Pharmacokinetics were assessed using noncompartmental methods.
  
  
  RESULTS
  Twenty-two GH-deficient children aged 6-16 yr were treated. Absorption of GH appeared to be faster after inhalation with maximum serum concentrations measured at 1-4 h compared with 2-8 h for sc GH. Mean relative bioavailability for inhaled GH was 3.5% (90% confidence interval 2.7-4.4%). Mean relative biopotency, based on IGF-I response, was 5.5% (confidence interval 5.2-5.8%). Similar dose-dependent increases in mean serum GH area under the curve and IGF-I changes from baseline were seen after inhaled and sc GH doses. Inhaled GH was well tolerated and preferred to injection. No significant changes in pulmonary function tests were seen.
  
  
  CONCLUSIONS
  In this first pediatric trial of GH delivered by inhalation, it was well tolerated and resulted in dose-dependent increases in serum GH and IGF-I levels. This study establishes that delivery of GH via the deep lung is feasible in children.
authors.affiliation: Department of Pediatrics (E.C.W.), Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ewalvoor@iupui.edu
authors.forename: Emily C
authors.initials: EC
authors.lastname: Walvoord
authors.forename: Amparo
authors.initials: A
authors.lastname: de la Peña
authors.forename: Soomin
authors.initials: S
authors.lastname: Park
authors.forename: Bernard
authors.initials: B
authors.lastname: Silverman
authors.forename: Leona
authors.initials: L
authors.lastname: Cuttler
authors.forename: Susan R
authors.initials: SR
authors.lastname: Rose
authors.forename: Gordon
authors.initials: G
authors.lastname: Cutler
authors.forename: Stenvert
authors.initials: S
authors.lastname: Drop
authors.forename: John J
authors.initials: JJ
authors.lastname: Chipman