Pharmacokinetics of Intraperitoneally Delivered Glucagon in Pigs: A Hypothesis of First Pass Metabolism
| Autor: | Ingrid Anna Teigen, Sven M. Carlsen, Sverre Christian Christiansen, Marte Kierulf Åm |
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| Rok vydání: | 2021 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Swine Clinical chemistry medicine.medical_treatment 030226 pharmacology & pharmacy Glucagon 03 medical and health sciences First pass effect 0302 clinical medicine Bolus (medicine) Pharmacokinetics Internal medicine Diabetes mellitus medicine Animals Pharmacology (medical) Original Research Article Pharmacology Dose-Response Relationship Drug Chemistry Insulin digestive oral and skin physiology medicine.disease Endocrinology Liver Area Under Curve 030220 oncology & carcinogenesis Female Injections Intraperitoneal hormones hormone substitutes and hormone antagonists Half-Life Hormone |
| Zdroj: | European journal of drug metabolism and pharmacokinetics European Journal of Drug Metabolism and Pharmacokinetics |
| ISSN: | 2107-0180 0378-7966 |
| DOI: | 10.1007/s13318-021-00692-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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