Post by compound26 on Jul 20, 2015 20:12:13 GMT -5
Even though not directly related to Afrezza, since Insulin is also a growth hormone, this sounds interesting to me. You can find the full report through the link below.
Inhaled Growth Hormone (GH) Compared with Subcutaneous GH in Children with GH Deficiency: Pharmacokinetics, Pharmacodynamics, and Safety
press.endocrine.org/doi/full/10.1210/jc.2008-1897
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.
Inhaled growth hormone administered to growth hormone deficient children for 7 days is well tolerated and results in dose-dependent increases in serum GH and IGF-1 levels.
Since GH replacement therapy was first reported in a child in 1958 (1) until now, injection has been the only method of administration. The need to administer human GH (hGH) by injection is associated with compliance issues (2, 3), avoidance of therapy (4, 5), and early termination of GH treatment (6). A 2005 study found that 23% of children taking hGH via needle and syringe missed more than three doses each month and 13% of children missed more than half of their prescribed doses over a 2-yr period (7). Despite advances in drug delivery over the past 2 decades, alternatives to injection have not been available for hGH. Because compliance is a significant problem in drug delivery to children (8), the development of an inhaled delivery system as an alternative to daily injection is appealing. The ultimate goal of such new delivery options would be improved compliance and patient satisfaction, leading to improved therapeutic efficacy.
Recent advances in aerosol technology, by increasing particle size and lowering their density and tendency to agglomerate, have increased efficiency of deep lung delivery and improved systemic absorption compared with conventional micronized particles (9). This has enabled development of an inhaled formulation of hGH, termed somatropin inhalation powder (SIP).
Before this study, SIP underwent a 6-month toxicology study in primates, pharmacokinetic (PK) and pharmacodynamic (PD) studies in healthy male adult subjects, and a 28-d pharmacokinetic and safety study in adults with mild to moderate asthma. All demonstrated acute safety and tolerability of SIP without any negative effects on pulmonary function tests (PFTs) (Ref. 10 and internal Lilly data). The current study is the first in children and was designed to assess safety, PK, and PD responses of SIP in children with GH deficiency (GHD) after inhalation of this new formulation of GH using a dry powder inhalation device.
The primary aims of this study were to estimate the relative bioavailability and biopotency between SIP and sc GH given as Humatrope (Hsc) and assess the safety and tolerability of SIP after multiple inhalations over a 1-wk period in pediatric patients. Secondary aims were to assess pulmonary function, PK and PD dose responses, and IGF-I and IGF binding protein (IGFBP)-3 levels after multiple doses of SIP. Device functionality was also assessed based on patient and dosing specialist report.
Inhaled Growth Hormone (GH) Compared with Subcutaneous GH in Children with GH Deficiency: Pharmacokinetics, Pharmacodynamics, and Safety
press.endocrine.org/doi/full/10.1210/jc.2008-1897
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.
Inhaled growth hormone administered to growth hormone deficient children for 7 days is well tolerated and results in dose-dependent increases in serum GH and IGF-1 levels.
Since GH replacement therapy was first reported in a child in 1958 (1) until now, injection has been the only method of administration. The need to administer human GH (hGH) by injection is associated with compliance issues (2, 3), avoidance of therapy (4, 5), and early termination of GH treatment (6). A 2005 study found that 23% of children taking hGH via needle and syringe missed more than three doses each month and 13% of children missed more than half of their prescribed doses over a 2-yr period (7). Despite advances in drug delivery over the past 2 decades, alternatives to injection have not been available for hGH. Because compliance is a significant problem in drug delivery to children (8), the development of an inhaled delivery system as an alternative to daily injection is appealing. The ultimate goal of such new delivery options would be improved compliance and patient satisfaction, leading to improved therapeutic efficacy.
Recent advances in aerosol technology, by increasing particle size and lowering their density and tendency to agglomerate, have increased efficiency of deep lung delivery and improved systemic absorption compared with conventional micronized particles (9). This has enabled development of an inhaled formulation of hGH, termed somatropin inhalation powder (SIP).
Before this study, SIP underwent a 6-month toxicology study in primates, pharmacokinetic (PK) and pharmacodynamic (PD) studies in healthy male adult subjects, and a 28-d pharmacokinetic and safety study in adults with mild to moderate asthma. All demonstrated acute safety and tolerability of SIP without any negative effects on pulmonary function tests (PFTs) (Ref. 10 and internal Lilly data). The current study is the first in children and was designed to assess safety, PK, and PD responses of SIP in children with GH deficiency (GHD) after inhalation of this new formulation of GH using a dry powder inhalation device.
The primary aims of this study were to estimate the relative bioavailability and biopotency between SIP and sc GH given as Humatrope (Hsc) and assess the safety and tolerability of SIP after multiple inhalations over a 1-wk period in pediatric patients. Secondary aims were to assess pulmonary function, PK and PD dose responses, and IGF-I and IGF binding protein (IGFBP)-3 levels after multiple doses of SIP. Device functionality was also assessed based on patient and dosing specialist report.
