Pharmacokinetics of Oral Levonorgestrel in Women After Roux-en-Y Gastric Bypass Surgery and in BMI-Matched Controls.

BACKGROUND

Women are advised to primarily use non-oral contraceptive alternatives after Roux-en-Y gastric bypass since it is not known if the surgery affects the pharmacokinetics of oral contraceptives.

METHODS

This is a multi-center, open label, phase 2 pharmacokinetic study performed at the University Hospital of Linköping and the Clinical Trials Center, Department of Obstetrics and Gynecology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. Fifteen women aged 18-40 years who had previously undergone Roux-en-Y gastric bypass surgery and reached a BMI < 30 were included. Fifteen BMI-matched women with no previous history of Roux-en-Y gastric bypass surgery served as a control group. After administration of a single dose of a combined oral contraceptive containing 0.03 mg ethinylestradiol/0.15 mg levonorgestrel, serum levonorgestrel concentrations were determined during a 24-h period using ultra performance liquid chromatography/tandem mass spectrometry. The area under the plasma concentration time curve of levonorgestrel (AUC) was the main outcome measure.

RESULTS

There were no significant differences in the studied pharmacokinetic parameters, AUC, total AUC, peak serum concentration (C), time to peak serum concentrations (T), apparent oral clearances of levonorgestrel (CL), or terminal half-lives (t½) between the groups.

CONCLUSION

This is to our knowledge the first study to evaluate the pharmacokinetics of oral levonorgestrel in women with a BMI < 30 at least 1 year after RYGB compared with a BMI-matched group of women. We could not find any significant pharmacokinetic differences between the groups, suggesting that oral levonorgestrel may be used in non-obese women after Roux-en-Y gastric bypass once a stable body weight has been reached.

CLINICAL TRIAL NUMBER

EudraCT 2014-004677-17.