Inhaled growth hormone (GH) compared with subcutaneous GH in children with gh deficiency

Pharmacokinetics, pharmacodynamics, and safety

Emily Walvoord, Amparo De La Peña, Soomin Park, Bernard Silverman, Leona Cuttler, Susan R. Rose, Gordon Cutler, Stenvert Drop, John J. Chipman

Research output: Contribution to journalArticle

40 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)2052-2059
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number6
DOIs
StatePublished - Jun 2009

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Pharmacodynamics
Pharmacokinetics
Growth Hormone
Safety
Insulin-Like Growth Factor I
Inhalation
Pediatrics
Biological Availability
Serum
Placebos
Confidence Intervals

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Inhaled growth hormone (GH) compared with subcutaneous GH in children with gh deficiency : Pharmacokinetics, pharmacodynamics, and safety. / Walvoord, Emily; De La Peña, Amparo; Park, Soomin; Silverman, Bernard; Cuttler, Leona; Rose, Susan R.; Cutler, Gordon; Drop, Stenvert; Chipman, John J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 6, 06.2009, p. 2052-2059.

Research output: Contribution to journalArticle

Walvoord, Emily ; De La Peña, Amparo ; Park, Soomin ; Silverman, Bernard ; Cuttler, Leona ; Rose, Susan R. ; Cutler, Gordon ; Drop, Stenvert ; Chipman, John J. / Inhaled growth hormone (GH) compared with subcutaneous GH in children with gh deficiency : Pharmacokinetics, pharmacodynamics, and safety. In: Journal of Clinical Endocrinology and Metabolism. 2009 ; Vol. 94, No. 6. pp. 2052-2059.
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AU - Silverman, Bernard

AU - Cuttler, Leona

AU - Rose, Susan R.

AU - Cutler, Gordon

AU - Drop, Stenvert

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N2 - 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.

AB - 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.

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