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Inhaled Growth Hormone (GH) Compared with Subcutaneous GH in Children with GH Deficiency: Pharmacokinetics, Pharmacodynamics, and Safety

Department of Pediatrics (E.C.W.), Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana 46202; Eli Lilly and Co. (A.d.l.P., S.P., G.C., J.J.C.), Indianapolis, Indiana 46285; Alkermes Inc. (B.S.), Cambridge, Massachusetts 02139; Department of Pediatrics (L.C.), Rainbow Babies and Children’s Hospital, Case Western Reserve University, Cleveland, Ohio 44106; Division of Pediatric Endocrinology (S.R.R.), Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229; and Division of Endocrinology (S.D.), Sophia Children’s Hospital, Erasmus Medical Centre, 3000-DR Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Emily C. Walvoord, 702 Barnhill Drive, Room 5960, Indianapolis, Indiana 46202. E-mail: ewalvoor{at}iupui.edu.

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.

Design/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.