Pharmacokinetic and pharmacodynamic modeling of exendin-4 in type 2 diabetic Goto-Kakizaki rats.

Gao W, Jusko WJ

The Journal of pharmacology and experimental therapeutics14 Dec 2010Cited by 37 (Europe PMC)

PMID21156817PMCIDPMC3061535DOI10.1124/jpet.110.175752PepBankPUB-21156817

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study9

5 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Pharmacokinetics
In diabetic Goto-Kakizaki rats, exendin‑4 rapidly disappeared from circulation after intravenous doses.
In plain wordsIn rats, exendin‑4 rapidly disappeared from blood after intravenous dosing.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseIntravenous disappearance
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki rats
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
0.5, 1, 5 or 10 μg/kg · intravenous · single doseAs given in this study (rat).
Source sentences
Summary
After intravenous doses, exendin-4 rapidly disappeared from the circulation,
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-2115681701
02AnimalAnimal study (in vivo)Pharmacokinetics
In diabetic Goto-Kakizaki rats, subcutaneous exendin‑4 showed rapid absorption with Tmax of 15-20 minutes.
In plain wordsIn rats, subcutaneous exendin‑4 reached its highest blood level after 15-20 minutes.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableSubcutaneous absorption Tmax
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki rats
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg/kg · subcutaneous · single doseAs given in this study (rat).
Measurements
Tmax
15 to 20 min
subcutaneous dose
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-2115681702
03AnimalAnimal study (in vivo)Pharmacokinetics
In diabetic Goto-Kakizaki rats, subcutaneous exendin‑4 had incomplete bioavailability of 0.51.
In plain wordsIn rats, subcutaneous exendin‑4 had incomplete bioavailability.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableSubcutaneous bioavailability
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki rats
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg/kg · subcutaneous · single doseAs given in this study (rat).
Measurements
Bioavailability
0.51 fraction
subcutaneous dose
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-2115681703
04AnimalAnimal study (in vivo)Mechanism
In diabetic Goto-Kakizaki rats, exendin‑4 increased insulin release, followed by rebound and a slow return to baseline.
In plain wordsIn rats, exendin‑4 increased insulin release, followed by a rebound and a slow return to baseline.
Peptide
Exenatide (exendin-4)
Outcome
MixedInsulin release time course
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · single doseAs given in this study (rat).
Measurements
Insulin release increase time
2 to 5 min
after exendin-4
Insulin rebound time
10 to 15 min
after exendin-4
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-2115681704
05AnimalAnimal study (in vivo)Efficacy outcome
In diabetic Goto-Kakizaki rats, glucose initially declined after exendin‑4, then gradually increased.
In plain wordsIn rats, blood sugar initially decreased after exendin‑4, then gradually increased.
Peptide
Exenatide (exendin-4)
Outcome
MixedGlucose time course
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · single doseAs given in this study (rat).
Source sentences
Summary
Glucose initially declined because of enhanced insulin secretion, and then gradually increased because of the activation of the neural system by exendin-4.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-2115681707

Studies that did not test the peptide alone4

In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Exenatide (exendin-4).

06Computer modelNot a test of Exenatide (exendin-4) aloneIn silicoMechanism
In rat-derived PK/PD modeling, exendin‑4 insulin release capacity S(max) was 6.91.
In plain wordsIn computer modeling from rat data, the exendin‑4 insulin release capacity parameter was 6.91.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableInsulin release capacity
Study
n: not reported in source
mechanistic PK/PD model from diabetic Goto-Kakizaki rat data
Outcome group
Receptor activity and mechanism · Pharmacology
Measurements
S(max)
6.91 unitless
insulin release capacity
Source sentences
Summary
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.
2 context sentences(design, population, supporting numbers)
Summary · context
Insulin turnover was characterized by an indirect response model with a precursor compartment.
Summary · context
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.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-2115681705
07Computer modelNot a test of Exenatide (exendin-4) aloneIn silicoMechanism
In rat-derived PK/PD modeling, exendin‑4 insulin release sensitivity SC₅₀ was 1.29 nM.
In plain wordsIn computer modeling from rat data, the exendin‑4 insulin release sensitivity parameter was 1.29 nM.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableInsulin release sensitivity
Study
n: not reported in source
mechanistic PK/PD model from diabetic Goto-Kakizaki rat data
Outcome group
Receptor activity and mechanism · Pharmacology
Measurements
SC50
1.29 nM
insulin release sensitivity
Source sentences
Summary
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.
2 context sentences(design, population, supporting numbers)
Summary · context
Insulin turnover was characterized by an indirect response model with a precursor compartment.
Summary · context
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.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-2115681706
08Computer modelNot a test of Exenatide (exendin-4) aloneIn silicoMechanism
In rat-derived PK/PD modeling, exendin‑4 hyperglycemic action used increased hepatic glucose production with S(RC) of 0.112 1/nM.
In plain wordsIn computer modeling from rat data, exendin‑4 increased liver glucose production with a fitted concentration-dependent factor.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseHepatic glucose production factor
Study
n: not reported in source
mechanistic PK/PD model from diabetic Goto-Kakizaki rat data
Outcome group
Receptor activity and mechanism · Liver
Measurements
S(RC)
0.112 1/nM
hepatic glucose production
Source sentences
Summary
The hyperglycemic action was modeled with increased hepatic glucose production with a linear factor S(RC) = 0.112 1/nM.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-2115681708
09Computer modelNot a test of Exenatide (exendin-4) aloneIn silicoOther
In rat-derived PK/PD modeling, the mechanistic model satisfactorily described exendin‑4 disposition and glucose and insulin effects.
In plain wordsIn computer modeling from rat data, the model satisfactorily described exendin‑4 drug levels and its glucose and insulin effects.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableModel fit
Study
n: not reported in source
mechanistic PK/PD model from diabetic Goto-Kakizaki rat data
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
The mechanistic PK/PD model satisfactorily described the disposition and effects of exendin-4 on glucose and insulin homeostasis in type 2 diabetic rats.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-2115681709

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
22 Oct 2026, 02:26 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

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