ArticlePharmaceutical research2012
Pharmacokinetic/pharmacodynamic modeling of GLP-1 in healthy rats.
Article in Pharmaceutical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 21 citations in OpenAlex.
- Opposing roles of the entero-pancreatic hormone urocortin-3 in glucose metabolism in rats.Diabetologia · 2022Article
- Multiple Selection Criteria for Probiotic Strains with High Potential for Obesity Management.Nutrients · 2021Article
- Exendin-4 reverses high glucose-induced endothelial progenitor cell dysfunction via SDF-1β/CXCR7-AMPK/p38-MAPK/IL-6 axis.Acta diabetologica · 2020Article
- Population pharmacodynamic modeling of exenatide after 2-week treatment in STZ/NA diabetic rats.Journal of pharmaceutical sciences · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo provide a mechanism-based model to quantitatively describe GLP-1 pharmacokinetics (PK) and pharmacodynamics (PD) in rats.
methodsIntravenous (IV), infusion (IF), subcutaneous (SC), and intraperitoneal (IP) doses of GLP-1 were administered after glucose challenge in healthy Sprague-Dawley rats. Blood was analyzed for GLP-1, glucose, and insulin. The PK-PD modeling was performed with ADAPT 5. The concentration-response curve was generated and analyzed in comparison with other incretin-related therapeutics.
resultsThe PK of GLP-1 was described using a two-compartment model with a zero-order input accounting for endogenous GLP-1 synthesis. For SC and IP dosing, sequential zero-order and first-order absorption models reasonably described the rapid absorption process and flip-flop kinetics. In dynamics, GLP-1 showed insulinotropic effects (3-fold increase) after IV glucose challenge in a dose-dependent manner. The concentration-response curve was bell-shaped, which was captured using a biphasic two-binding site Adair model. Receptor binding of GLP-1 exhibited high capacity and low affinity kinetics for both binding sites (K(D) = 9.94 × 10(3) pM, K(2) = 1.56 × 10(-4) pM(-1)).
conclusionsThe PK of GLP-1 was linear and bi-exponential and its PD showed glucose-dependent insulinotropic effects. All profiles were captured by the present mechanistic model and the dynamic analysis yields several implications for incretin-related therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.