Effect of renal impairment on the pharmacokinetics of exenatide.

Linnebjerg H, Kothare PA, Park S, Mace K, Reddy S, Mitchell M, Lins R

British journal of clinical pharmacology10 Apr 2007Cited by 132 (Europe PMC)

PMID17425627PMCIDPMC2000650DOI10.1111/j.1365-2125.2007.02890.xPepBankPUB-17425627

Summary

AimsTo evaluate the pharmacokinetics (PK), safety and tolerability of a single exenatide dose in patients with renal impairment (RI).MethodsExenatide (5 or 10 microg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function [Cockcroft-Gault creatinine clearance (CrCL), number of subjects]: normal (>80 ml min(-1), n = 8), mild RI (51-80 ml min(-1), n = 8), moderate RI (31-50 ml min(-1), n = 7) or end-stage renal disease (ESRD) requiring haemodialysis (n = 8). PK data were combined with four previous single-dose studies in patients with Type 2 diabetes to explore the relationship of exenatide clearance (CLp/F) and CrCL.ResultsMean half-life for healthy, mild RI, moderate RI and ESRD groups were 1.5, 2.1, 3.2 and 6.0 h, respectively. After combining data from multiple studies, least squares geometric means for CLp/F in subjects with normal renal function, mild RI, moderate RI and ESRD were 8.14, 5.19, 7.11 and 1.3 l h(-1), respectively. Exenatide was generally well tolerated in the mild and moderate RI groups, but not in subjects with ESRD due to nausea and vomiting. Simulations of exenatide plasma concentrations also suggest patients with ESRD should have a propensity for poor tolerability at the lowest available therapeutic dosage (5 microg q.d.).ConclusionsSince tolerability and PK changes were considered clinically acceptable in patients with mild to moderate RI, it would be appropriate to administer exenatide to these patients without dosage adjustment. However, poor tolerability and significant changes in PK make the currently available therapeutic doses (5 and 10 microg) unsuitable in severe RI or ESRD.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study11

10 results from studies that gave the peptide. 10 results from people.

01HumanNon-randomized trialSafety outcome
Exenatide was generally well tolerated in subjects with mild or moderate renal impairment.
In plain wordsPeople with mild or moderate kidney impairment generally tolerated exenatide.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableTolerability mild and moderate renal impairment
Study
n = 15
Outcome group
Adverse events · Pharmacology
Studied dose
5 or 10 microg · subcutaneous · single doseAs given in this study (human).
Source sentences
Summary
Exenatide was generally well tolerated in the mild and moderate RI groups, but not in subjects with ESRD due to nausea and vomiting.
1 context sentence(design, population, supporting numbers)
Summary · context
Exenatide (5 or 10 microg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function
Show in the study text Report a problemFND-1742562709
02HumanNon-randomized trialPharmacokinetics
In subjects with normal renal function, exenatide had a mean half-life of 1.5 h.
In plain wordsExenatide had a mean half-life of 1.5 hours in people with normal kidney function.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableHalf-life normal renal function
Study
n = 8
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 or 10 microg · subcutaneous · single doseAs given in this study (human).
Measurements
Half-life
1.5 h
normal renal function
Source sentences
Summary
Mean half-life for healthy, mild RI, moderate RI and ESRD groups were 1.5, 2.1, 3.2 and 6.0 h, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Exenatide (5 or 10 microg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function
Show in the study text Report a problemFND-1742562701
03HumanNon-randomized trialPharmacokinetics
In subjects with mild renal impairment, exenatide had a mean half-life of 2.1 h.
In plain wordsExenatide had a mean half-life of 2.1 hours in people with mild kidney impairment.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableHalf-life mild renal impairment
Study
n = 8
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 or 10 microg · subcutaneous · single doseAs given in this study (human).
Measurements
Half-life
2.1 h
mild RI
Source sentences
Summary
Mean half-life for healthy, mild RI, moderate RI and ESRD groups were 1.5, 2.1, 3.2 and 6.0 h, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Exenatide (5 or 10 microg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function
Show in the study text Report a problemFND-1742562702
04HumanNon-randomized trialPharmacokinetics
In subjects with ESRD, exenatide had a mean half-life of 6.0 h.
In plain wordsExenatide had a mean half-life of 6.0 hours in people with end-stage kidney disease.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableHalf-life ESRD
Study
n = 8
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 or 10 microg · subcutaneous · single doseAs given in this study (human).
Measurements
Half-life
6 h
ESRD
Source sentences
Summary
Mean half-life for healthy, mild RI, moderate RI and ESRD groups were 1.5, 2.1, 3.2 and 6.0 h, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Exenatide (5 or 10 microg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function
Show in the study text Report a problemFND-1742562704
05HumanNon-randomized trialSafety outcome
In subjects with ESRD, a single exenatide dose was not well tolerated due to nausea and vomiting.
In plain wordsPeople with end-stage kidney disease did not tolerate a single exenatide dose well because of nausea and vomiting.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableTolerability in ESRD (nausea and vomiting)
Study
n = 8
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
5 or 10 microg · subcutaneous · single doseAs given in this study (human).
Source sentences
Summary
Exenatide was generally well tolerated in the mild and moderate RI groups, but not in subjects with ESRD due to nausea and vomiting.
1 context sentence(design, population, supporting numbers)
Summary · context
Exenatide (5 or 10 microg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function
Show in the study text Report a problemFND-1742562710
06HumanNon-randomized trialPharmacokinetics
In subjects with moderate renal impairment, exenatide had a mean half-life of 3.2 h.
In plain wordsExenatide had a mean half-life of 3.2 hours in people with moderate kidney impairment.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableHalf-life moderate renal impairment
Study
n = 7
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 or 10 microg · subcutaneous · single doseAs given in this study (human).
Measurements
Half-life
3.2 h
moderate RI
Source sentences
Summary
Mean half-life for healthy, mild RI, moderate RI and ESRD groups were 1.5, 2.1, 3.2 and 6.0 h, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Exenatide (5 or 10 microg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function
Show in the study text Report a problemFND-1742562703
07HumanNon-randomized trialPharmacokinetics
In pooled studies, exenatide clearance in normal renal function was 8.14 l h(-1).
In plain wordsExenatide clearance was 8.14 liters per hour in people with normal kidney function across pooled studies.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableClearance normal renal function
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · single doseAs given in this study (human).
Measurements
CLp/F
8.14 l h(-1)
normal renal function
Source sentences
Summary
After combining data from multiple studies, least squares geometric means for CLp/F in subjects with normal renal function, mild RI, moderate RI and ESRD were 8.14, 5.19, 7.11 and 1.3 l h(-1), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
PK data were combined with four previous single-dose studies in patients with Type 2 diabetes to explore the relationship of exenatide clearance (CLp/F) and CrCL.
Show in the study text Report a problemFND-1742562705
08HumanNon-randomized trialPharmacokinetics
In pooled studies, exenatide clearance in mild renal impairment was 5.19 l h(-1).
In plain wordsExenatide clearance was 5.19 liters per hour in people with mild kidney impairment across pooled studies.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableClearance mild renal impairment
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · single doseAs given in this study (human).
Measurements
CLp/F
5.19 l h(-1)
mild RI
Source sentences
Summary
After combining data from multiple studies, least squares geometric means for CLp/F in subjects with normal renal function, mild RI, moderate RI and ESRD were 8.14, 5.19, 7.11 and 1.3 l h(-1), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
PK data were combined with four previous single-dose studies in patients with Type 2 diabetes to explore the relationship of exenatide clearance (CLp/F) and CrCL.
Show in the study text Report a problemFND-1742562706
09HumanNon-randomized trialPharmacokinetics
In pooled studies, exenatide clearance in moderate renal impairment was 7.11 l h(-1).
In plain wordsExenatide clearance was 7.11 liters per hour in people with moderate kidney impairment across pooled studies.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableClearance moderate renal impairment
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · single doseAs given in this study (human).
Measurements
CLp/F
7.11 l h(-1)
moderate RI
Source sentences
Summary
After combining data from multiple studies, least squares geometric means for CLp/F in subjects with normal renal function, mild RI, moderate RI and ESRD were 8.14, 5.19, 7.11 and 1.3 l h(-1), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
PK data were combined with four previous single-dose studies in patients with Type 2 diabetes to explore the relationship of exenatide clearance (CLp/F) and CrCL.
Show in the study text Report a problemFND-1742562707
10HumanNon-randomized trialPharmacokinetics
In pooled studies, exenatide clearance in ESRD was 1.3 l h(-1).
In plain wordsExenatide clearance was 1.3 liters per hour in people with end-stage kidney disease across pooled studies.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableClearance ESRD
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · single doseAs given in this study (human).
Measurements
CLp/F
1.3 l h(-1)
ESRD
Source sentences
Summary
After combining data from multiple studies, least squares geometric means for CLp/F in subjects with normal renal function, mild RI, moderate RI and ESRD were 8.14, 5.19, 7.11 and 1.3 l h(-1), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
PK data were combined with four previous single-dose studies in patients with Type 2 diabetes to explore the relationship of exenatide clearance (CLp/F) and CrCL.
Show in the study text Report a problemFND-1742562708

Studies that did not test the peptide alone1

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).

11Computer modelNot a test of Exenatide (exendin-4) aloneIn silicoSafety outcome
Simulated exenatide concentrations suggested poor tolerability in ESRD at the lowest therapeutic dosage.
In plain wordsComputer predictions suggested poor exenatide tolerance in end-stage kidney disease even at the lowest therapeutic dose.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableSimulated ESRD tolerability
Study
n: not reported in source
Outcome group
Adverse events · Pharmacology
Source sentences
Summary
Simulations of exenatide plasma concentrations also suggest patients with ESRD should have a propensity for poor tolerability at the lowest available therapeutic dosage (5 microg q.d.).
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).
Show in the study text Report a problemFND-1742562712

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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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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Effect of renal impairment on the pharmacokinetics of exenatide.

Summary

Results from this study11

Studies that did not test the peptide alone1

Version history

Subjects

Publication types

MeSH terms