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Pharmacokinetics of Intraperitoneally Delivered Glucagon in Pigs: A Hypothesis of First Pass Metabolism

BACKGROUND AND OBJECTIVE: Artificial pancreases administering low-dose glucagon in addition to insulin have the scope to improve glucose control in patients with diabetes mellitus type 1. If such a device were to deliver both hormones intraperitoneally, it would mimic normal physiology, which may be...

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Autores principales: Teigen, Ingrid Anna, Åm, Marte Kierulf, Carlsen, Sven Magnus, Christiansen, Sverre Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298214/
https://www.ncbi.nlm.nih.gov/pubmed/34100220
http://dx.doi.org/10.1007/s13318-021-00692-2
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author Teigen, Ingrid Anna
Åm, Marte Kierulf
Carlsen, Sven Magnus
Christiansen, Sverre Christian
author_facet Teigen, Ingrid Anna
Åm, Marte Kierulf
Carlsen, Sven Magnus
Christiansen, Sverre Christian
author_sort Teigen, Ingrid Anna
collection PubMed
description BACKGROUND AND OBJECTIVE: Artificial pancreases administering low-dose glucagon in addition to insulin have the scope to improve glucose control in patients with diabetes mellitus type 1. If such a device were to deliver both hormones intraperitoneally, it would mimic normal physiology, which may be beneficial. However, the pharmacokinetic properties of glucagon after intraperitoneal administration are not well known. Hence, the current study aims to evaluate the relationship between the amount of intraperitoneally delivered glucagon and pharmacokinetic variables in a pig model. METHODS: Pharmacokinetic data was retrieved from experiments on 19 anaesthetised pigs and analysed post hoc. The animals received a single intraperitoneal bolus of glucagon ranging from 0.30 to 4.46 µg/kg. Plasma glucagon was measured every 2–10 min for 50 min. RESULTS: Peak plasma concentration and area under the time–plasma concentration curve of glucagon correlated positively with the administered dose, and larger boluses provided a relatively greater increase. The mean (standard deviation) time to maximum glucagon concentration in plasma was 11 (5) min, and the mean elimination half-life of glucagon in plasma was 19 (7) min. CONCLUSIONS: Maximum plasma concentration and area under the time–plasma concentration curve of glucagon increase nonlinearly in relation to the intraperitoneally administered glucagon dose. We hypothesise that the results are compatible with a satiable first-pass metabolism in the liver. Time to maximum glucagon concentration in plasma and the elimination half-life of glucagon in plasma seem independent of the drug dose.
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spelling pubmed-82982142021-07-23 Pharmacokinetics of Intraperitoneally Delivered Glucagon in Pigs: A Hypothesis of First Pass Metabolism Teigen, Ingrid Anna Åm, Marte Kierulf Carlsen, Sven Magnus Christiansen, Sverre Christian Eur J Drug Metab Pharmacokinet Original Research Article BACKGROUND AND OBJECTIVE: Artificial pancreases administering low-dose glucagon in addition to insulin have the scope to improve glucose control in patients with diabetes mellitus type 1. If such a device were to deliver both hormones intraperitoneally, it would mimic normal physiology, which may be beneficial. However, the pharmacokinetic properties of glucagon after intraperitoneal administration are not well known. Hence, the current study aims to evaluate the relationship between the amount of intraperitoneally delivered glucagon and pharmacokinetic variables in a pig model. METHODS: Pharmacokinetic data was retrieved from experiments on 19 anaesthetised pigs and analysed post hoc. The animals received a single intraperitoneal bolus of glucagon ranging from 0.30 to 4.46 µg/kg. Plasma glucagon was measured every 2–10 min for 50 min. RESULTS: Peak plasma concentration and area under the time–plasma concentration curve of glucagon correlated positively with the administered dose, and larger boluses provided a relatively greater increase. The mean (standard deviation) time to maximum glucagon concentration in plasma was 11 (5) min, and the mean elimination half-life of glucagon in plasma was 19 (7) min. CONCLUSIONS: Maximum plasma concentration and area under the time–plasma concentration curve of glucagon increase nonlinearly in relation to the intraperitoneally administered glucagon dose. We hypothesise that the results are compatible with a satiable first-pass metabolism in the liver. Time to maximum glucagon concentration in plasma and the elimination half-life of glucagon in plasma seem independent of the drug dose. Springer International Publishing 2021-06-07 2021 /pmc/articles/PMC8298214/ /pubmed/34100220 http://dx.doi.org/10.1007/s13318-021-00692-2 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original Research Article
Teigen, Ingrid Anna
Åm, Marte Kierulf
Carlsen, Sven Magnus
Christiansen, Sverre Christian
Pharmacokinetics of Intraperitoneally Delivered Glucagon in Pigs: A Hypothesis of First Pass Metabolism
title Pharmacokinetics of Intraperitoneally Delivered Glucagon in Pigs: A Hypothesis of First Pass Metabolism
title_full Pharmacokinetics of Intraperitoneally Delivered Glucagon in Pigs: A Hypothesis of First Pass Metabolism
title_fullStr Pharmacokinetics of Intraperitoneally Delivered Glucagon in Pigs: A Hypothesis of First Pass Metabolism
title_full_unstemmed Pharmacokinetics of Intraperitoneally Delivered Glucagon in Pigs: A Hypothesis of First Pass Metabolism
title_short Pharmacokinetics of Intraperitoneally Delivered Glucagon in Pigs: A Hypothesis of First Pass Metabolism
title_sort pharmacokinetics of intraperitoneally delivered glucagon in pigs: a hypothesis of first pass metabolism
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298214/
https://www.ncbi.nlm.nih.gov/pubmed/34100220
http://dx.doi.org/10.1007/s13318-021-00692-2
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