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

BMC Clinical Pharmacology

Helle Linnebjerg²  Malcolm I Mitchell¹  Kenneth Mace¹  Justin Northrup¹  Mary E Seger¹  Prajakti A Kothare¹ 

[1] Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA;Eli Lilly and Company, Lilly Research Center, Earl Wood Manor, Windlesham, Surrey GU20 6PH, UK

关键词: oral contraceptive;    pharmacokinetics;    exenatide twice daily;   

Others  :  860785
DOI  :  10.1186/1472-6904-12-8

 received in 2011-09-23, accepted in 2012-03-19,  发布年份 2012

【 摘 要 】

Background

Consistent 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 (C_max). This study evaluated the drug interaction potential of exenatide when administered adjunctively with oral contraceptives, given their potential concomitant use.

Methods

This 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.

Results

Exenatide 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) C_max 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 C_max 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.

Conclusions

The observed reduction in C_max 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 registration

ClinicalTrials.gov: NCT00254800.

【 授权许可】

   
2012 Kothare et al; licensee BioMed Central Ltd.

【 图 表 】

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