Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial.

Kothare PA, Seger ME, Northrup J, Mace K, Mitchell MI, Linnebjerg H

BMC clinical pharmacology19 Mar 2012Cited by 23 (Europe PMC)

PMID22429273PMCIDPMC3378442DOI10.1186/1472-6904-12-8PepBankPUB-22429273

Summary

BackgroundConsistent with its effect on gastric emptying, exenatide, an injectable treatment for type 2 diabetes, may slow the absorption rate of concomitantly administered oral drugs resulting in a decrease in maximum concentration (Cmax). This study evaluated the drug interaction potential of exenatide when administered adjunctively with oral contraceptives, given their potential concomitant use.MethodsThis trial evaluated the effect of exenatide co-administration on single- and multiple-dose pharmacokinetics of a combination oral contraceptive (ethinyl estradiol [EE] 30 μg, levonorgestrel [LV] 150 μg [Microgynon 30®]). Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide). Subjects received a single dose of oral contraceptive on Day 8 of each period and QD doses on Days 10 through 28. During treatment periods of concomitant usage, exenatide was administered subcutaneously prior to morning and evening meals at 5 μg BID from Days 1 through 4 and at 10 μg BID from Days 5 through 22. Single- (Day 8) and multiple-dose (Day 22) pharmacokinetic profiles were assessed for each treatment period.ResultsExenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral contraceptive component. No substantive changes in oral contraceptive pharmacokinetics occurred when oral contraceptive was administered 1 hour before exenatide. Single-dose oral contraceptive administration 30 minutes after exenatide resulted in mean (90% CI) Cmax reductions of 46% (42-51%) and 41% (35-47%) for EE and LV, respectively. Repeated daily oral contraceptive administration 30 minutes after exenatide resulted in Cmax reductions of 45% (40-50%) and 27% (21-33%) for EE and LV, respectively. Peak oral contraceptive concentrations were delayed approximately 3 to 4 hours. Mild-to-moderate nausea and vomiting were the most common adverse events observed during the trial.ConclusionsThe observed reduction in Cmax is likely of limited importance given the unaltered oral contraceptive bioavailability and trough concentrations; however, for oral medications that are dependent on threshold concentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs at least 1 hour before exenatide injection.Trial registrationClinicalTrials.gov: NCT00254800.

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

Results from this study12

12 results from studies that gave the peptide. 12 results from people.

01HumanRandomized controlled trialPharmacokinetics
In healthy women, exenatide did not alter ethinyl estradiol bioavailability.
In plain wordsIn healthy women, exenatide did not change ethinyl estradiol bioavailability compared with contraceptive alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeEthinyl estradiol bioavailability
Study
n = 32
Comparator
Oral contraceptive alone
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Source sentences
Summary
Exenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral contraceptive component.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927301
02HumanRandomized controlled trialPharmacokinetics
In healthy women, exenatide did not alter levonorgestrel bioavailability.
In plain wordsIn healthy women, exenatide did not change levonorgestrel bioavailability compared with contraceptive alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeLevonorgestrel bioavailability
Study
n = 32
Comparator
Oral contraceptive alone
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Source sentences
Summary
Exenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral contraceptive component.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927302
03HumanRandomized controlled trialPharmacokinetics
In healthy women, exenatide did not decrease daily ethinyl estradiol trough concentrations.
In plain wordsIn healthy women, exenatide did not reduce daily minimum ethinyl estradiol levels compared with contraceptive alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeEthinyl estradiol trough concentration
Study
n = 32
Comparator
Oral contraceptive alone
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Source sentences
Summary
Exenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral contraceptive component.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927303
04HumanRandomized controlled trialPharmacokinetics
In healthy women, exenatide did not decrease daily levonorgestrel trough concentrations.
In plain wordsIn healthy women, exenatide did not reduce daily minimum levonorgestrel levels compared with contraceptive alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeLevonorgestrel trough concentration
Study
n = 32
Comparator
Oral contraceptive alone
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Source sentences
Summary
Exenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral contraceptive component.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927304
05HumanRandomized controlled trialPharmacokinetics
In healthy women, contraceptive pharmacokinetics did not change substantively when taken before exenatide.
In plain wordsIn healthy women, contraceptive handling did not change substantively when taken before exenatide, compared with contraceptive alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeContraceptive pharmacokinetics before exenatide
Study
n = 32
Comparator
Oral contraceptive alone
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Source sentences
Summary
No substantive changes in oral contraceptive pharmacokinetics occurred when oral contraceptive was administered 1 hour before exenatide.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927305
06HumanRandomized controlled trialPharmacokinetics
In healthy women, single-dose ethinyl estradiol Cmax decreased when taken after exenatide.
In plain wordsIn healthy women, peak ethinyl estradiol levels decreased after exenatide compared with contraceptive alone.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseSingle-dose ethinyl estradiol Cmax
Study
n = 32
Comparator
Oral contraceptive alone
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Measurements
Cmax reduction
46%
Single-dose EE after exenatide
Source sentences
Summary
Single-dose oral contraceptive administration 30 minutes after exenatide resulted in mean (90% CI) Cmax reductions of 46% (42-51%) and 41% (35-47%) for EE and LV, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927306
07HumanRandomized controlled trialPharmacokinetics
In healthy women, single-dose levonorgestrel Cmax decreased when taken after exenatide.
In plain wordsIn healthy women, peak levonorgestrel levels decreased after exenatide compared with contraceptive alone.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseSingle-dose levonorgestrel Cmax
Study
n = 32
Comparator
Oral contraceptive alone
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Measurements
Cmax reduction
41%
Single-dose LV after exenatide
Source sentences
Summary
Single-dose oral contraceptive administration 30 minutes after exenatide resulted in mean (90% CI) Cmax reductions of 46% (42-51%) and 41% (35-47%) for EE and LV, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927307
08HumanRandomized controlled trialPharmacokinetics
In healthy women, repeated-dose ethinyl estradiol Cmax decreased when taken after exenatide.
In plain wordsIn healthy women, repeated contraceptive doses produced lower peak ethinyl estradiol levels after exenatide than contraceptive alone.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseRepeated-dose ethinyl estradiol Cmax
Study
n = 32
Comparator
Oral contraceptive alone
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Measurements
Cmax reduction
45%
Repeated-dose EE after exenatide
Source sentences
Summary
Repeated daily oral contraceptive administration 30 minutes after exenatide resulted in Cmax reductions of 45% (40-50%) and 27% (21-33%) for EE and LV, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927308
09HumanRandomized controlled trialPharmacokinetics
In healthy women, repeated-dose levonorgestrel Cmax decreased when taken after exenatide.
In plain wordsIn healthy women, repeated contraceptive doses produced lower peak levonorgestrel levels after exenatide than contraceptive alone.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseRepeated-dose levonorgestrel Cmax
Study
n = 32
Comparator
Oral contraceptive alone
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Measurements
Cmax reduction
27%
Repeated-dose LV after exenatide
Source sentences
Summary
Repeated daily oral contraceptive administration 30 minutes after exenatide resulted in Cmax reductions of 45% (40-50%) and 27% (21-33%) for EE and LV, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927309
10HumanRandomized controlled trialPharmacokinetics
In healthy women, exenatide delayed peak contraceptive concentrations by approximately 3 to 4 hours.
In plain wordsIn healthy women, peak contraceptive levels occurred later with exenatide than with contraceptive alone.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseTime to peak contraceptive concentration
Study
n = 32
Comparator
Oral contraceptive alone
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Measurements
Delay in peak contraceptive concentration
3 to 4 hours
Oral contraceptive after exenatide
Source sentences
Summary
Peak oral contraceptive concentrations were delayed approximately 3 to 4 hours.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927310
11HumanRandomized controlled trialSafety outcome
In healthy women, mild-to-moderate nausea was among the most common adverse events during the exenatide interaction trial.
In plain wordsIn healthy women, mild-to-moderate nausea was among the most common adverse events during the trial.
Peptide
Exenatide (exendin-4)
Outcome
Direction not reportedNausea
Study
n = 32
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Source sentences
Summary
Mild-to-moderate nausea and vomiting were the most common adverse events observed during the trial.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927311
12HumanRandomized controlled trialSafety outcome
In healthy women, mild-to-moderate vomiting was among the most common adverse events during the exenatide interaction trial.
In plain wordsIn healthy women, mild-to-moderate vomiting was among the most common adverse events during the trial.
Peptide
Exenatide (exendin-4)
Outcome
Direction not reportedVomiting
Study
n = 32
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
5 μg BID Days 1-4; 10 μg BID Days 5-22 · subcutaneousAs given in this study (human).
Source sentences
Summary
Mild-to-moderate nausea and vomiting were the most common adverse events observed during the trial.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide).
Show in the study text Report a problemFND-2242927312

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

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 1NCT00254800

The Effects of Exenatide on Oral Contraceptive Pharmacokinetics in Healthy Females

AstraZenecan = 38Nov 2005 to Aug 2006

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 18 Aug 2015

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

Subjects

Terms as the source lists them.

Publication types

MeSH terms

PepBank is a research reference. Talk to a doctor before you use any peptide.