ArticleThe Journal of pharmacology and experimental therapeutics2011
Pharmacokinetic and pharmacodynamic modeling of exendin-4 in type 2 diabetic Goto-Kakizaki rats.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Mechanism-based population modelling of the effects of vildagliptin on GLP-1, glucose and insulin in patients with type 2 diabetes.British journal of clinical pharmacology · 2012Trial
- Local depletion of large molecule drugs due to target binding in tissue interstitial space.CPT: pharmacometrics & systems pharmacology · 2024Review
- Variation in responses to incretin therapy: Modifiable and non-modifiable factors.Frontiers in molecular biosciences · 2023Review
- Electrochemical Sensing of the Peptide Drug Exendin-4 Using a Versatile Nucleic Acid Nanostructure.ACS sensors · 2022Article
- Exendin-4 as a Versatile Therapeutic Agent for the Amelioration of Diabetic Changes.Advanced pharmaceutical bulletin · 2022Review
- Glucagon-like peptide-1 in diabetes care: Can glycaemic control be achieved without nausea and vomiting?British journal of pharmacology · 2022Review
- Pharmacokinetic-pharmacodynamic modelling of the hypoglycaemic effect of pulsatile administration of human insulin in rats.Scientific reports · 2020Article
- A second-generation glucagon-like peptide-1 receptor agonist mitigates vomiting and anorexia while retaining glucoregulatory potency in lean diabetic and emetic mammalian models.Diabetes, obesity & metabolism · 2020Article
- Targeting GLP-1 receptor trafficking to improve agonist efficacy.Nature communications · 2018Article
- Review of Pharmacokinetic Data of Different Drug Classes in Goto-Kakizaki Rats, a Non-obese Model for Type 2 Diabetes Mellitus: Case Studies and Perspectives.European journal of drug metabolism and pharmacokinetics · 2017Review
- Population pharmacokinetics of exenatide.British journal of clinical pharmacology · 2017Article
- A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity.Bioconjugate chemistry · 2016Article
- Utilization of model-based meta-analysis to delineate the net efficacy of taspoglutide from the response of placebo in clinical trials.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2015Article
- A Tutorial on Target-Mediated Drug Disposition (TMDD) Models.CPT: pharmacometrics & systems pharmacology · 2015Article
- In vitro metabolic stability of exendin-4: pharmacokinetics and identification of cleavage products.PloS one · 2015Article
- Population pharmacodynamic modeling of exenatide after 2-week treatment in STZ/NA diabetic rats.Journal of pharmaceutical sciences · 2013Article
- Pharmacokinetics and pharmacokinetic-pharmacodynamic correlations of therapeutic peptides.Clinical pharmacokinetics · 2013Review
- Interspecies modeling and prediction of human exenatide pharmacokinetics.Pharmaceutical research · 2013Article
- Pharmacokinetic/pharmacodynamic studies on exenatide in diabetic rats.Acta pharmacologica Sinica · 2012Article
- Target-mediated pharmacokinetic and pharmacodynamic model of exendin-4 in rats, monkeys, and humans.Drug metabolism and disposition: the biological fate of chemicals · 2012Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
The pharmacokinetics (PK) and pharmacodynamics (PD) of exendin-4 were studied in type 2 diabetic Goto-Kakizaki rats after single doses at 0.5, 1, 5, or 10 μg/kg by intravenous administration and 5 μg/kg by subcutaneous administration. Plasma exendin-4, glucose, and insulin concentrations were determined. A target-mediated drug disposition model was used to characterize the PK of exendin-4. Glucose turnover was described by an indirect response model, with insulin stimulating glucose disposition. Insulin turnover was characterized by an indirect response model with a precursor compartment. After intravenous doses, exendin-4 rapidly disappeared from the circulation, whereas it exhibited rapid absorption (T(max) = 15-20 min) and incomplete bioavailability (F = 0.51) after the subcutaneous dose. Exendin-4 increased insulin release at 2 to 5 min with capacity S(max) = 6.91 and sensitivity SC₅₀ = 1.29 nM, followed by a rebound at 10 to 15 min and a slow return to the baseline. Glucose initially declined because of enhanced insulin secretion, and then gradually increased because of the activation of the neural system by exendin-4. The hyperglycemic action was modeled with increased hepatic glucose production with a linear factor S(RC) = 0.112 1/nM. The mechanistic PK/PD model satisfactorily described the disposition and effects of exendin-4 on glucose and insulin homeostasis in type 2 diabetic rats.
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