Broad variability in pharmacokinetics of GH following rhGH injections in children.
Growth Horm IGF Res
; 40: 61-68, 2018 06.
Article
em En
| MEDLINE
| ID: mdl-29422321
ABSTRACT
OBJECTIVE:
Daily subcutaneous self-injection of GH is used worldwide to treat short stature in childhood; longitudinal data on the impact of this regimen on GH-uptake are lacking.DESIGN:
Children with/without GH-deficiency participating in clinical trials were followed prospectively (≤8 times). Blood was sampled pre-GH-injection (dose GH33/GH67⯵g/kg) and either every 30â¯min thereafter for 24â¯h (Experimental-setting; 59 GH-curves/15 children); or every 2â¯h thereafter for 16â¯h (Clinical-setting; 429 GH-curves/117 children). Pharmacokinetics were estimated by time Tmax (h) of maximal GH-concentration (Cmax, mU/L) and area under the curve for 16â¯h (AUC, mU/Lâ¯∗â¯h).RESULTS:
In the Clinical-setting, median Cmax was 71â¯mU/L and AUC was 534â¯mU/Lâ¯∗â¯h, with coefficients of variation for intra-individual variation of 39% and 36%, respectively, and inter-individual variation of 44% and 42%, respectively. 43% of Cmax and AUC variability was explained by GH-dose and proxies for injection depth (baseline GH-level, GHpeakwidth, BMISDS). In the Experimental- versus Clinical-setting, 85% and 40% of GH-curves, respectively, reached zero-levels within 24â¯h. A longer duration was found following a more superficial GH-injection. Spontaneous GH-peaks were identified already 6â¯h after the GH-injection in about half of the curves of both GHD and non-GHD patients.CONCLUSION:
Very broad intra-individual and inter-individual variability was found. A high GH-peak will optimize growth effects; the highest Cmax was found after a deep injection of GH at the higher dose and concentration. In as many as 60% of the children, GH remained detectable in serum after 24â¯h; a constant GH-level will promote IGF-I and metabolic effects.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes
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Hormônio do Crescimento Humano
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Transtornos do Crescimento
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Growth Horm IGF Res
Ano de publicação:
2018
Tipo de documento:
Article