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Tong, J.* ; Dave, N.* ; Mugundu, G.M.* ; Davis, H.W.* ; Gaylinn, B.D.* ; Thorner, M.O.* ; Tschöp, M.H. ; D'Alessio, D.* ; Desai, P.B.*

The pharmacokinetics of acyl, des-acyl, and total ghrelin in healthy human subjects.

Eur. J. Endocrinol. 168, 821-828 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Background: Ghrelin stimulates GH secretion and regulates energy and glucose metabolism. The two circulating isoforms, acyl (AG) and des-acyl (DAG) ghrelin, have distinct metabolic effects and are under active investigation for their therapeutic potentials. However, there is only limited data on the pharmacokinetics of AG and DAG. Objectives: To evaluate key pharmacokinetic parameters of AG, DAG, and total ghrelin in healthy men and women. Methods: In study 1, AG (1, 3, and 5 mu g/kg per h) was infused over 65 min in 12 healthy (8 F/4 M) subjects in randomized order. In study 2, AG (1 mg/kg per h), DAG (4 mu g/kg per h), or both were infused over 210 min in ten healthy individuals (5 F/5 M). Plasma AG and DAG were measured using specific two-site ELISAs (study 1 and 2), and total ghrelin with a commercial RIA (study 1). Pharmacokinetic parameters were estimated by non-compartmental analysis. Results: After the 1, 3, and 5 mu g/kg per h doses of AG, there was a dose-dependent increase in the maximum concentration (C-max) and area under the curve (AUC((0-last))) of AG and total ghrelin. Among the different AG doses, there was no difference in the elimination half-life, systemic clearance (CL), and volume of distribution. DAG had decreased CL relative to AG. The plasma DAG: AG ratio was similar to 2:1 during steady-state infusion of AG. Infusion of AG caused an increase in DAG, but DAG administration did not change plasma AG. Ghrelin administration did not affect plasma acylase activity. Conclusions: The pharmacokinetics of AG and total ghrelin appears to be linear and proportional in the dose range tested. AG and DAG have very distinct metabolic fates in the circulation. There is deacylation of AG in the plasma but no evidence of acylation.
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Hormone Secretagogue Receptor ; Unacylated Ghrelin ; Plasma Ghrelin ; Human Pancreas ; Renal-failure ; Young Men ; In-vitro ; Glucose ; Growth ; Endocrine
ISSN (print) / ISBN 0804-4643
e-ISSN 1479-683X
Quellenangaben Volume: 168, Issue: 6, Pages: 821-828 Article Number: , Supplement: ,
Publisher BioScientifica
Non-patent literature Publications
Reviewing status Peer reviewed