Abstract
Objective
To determine if differences exist in the pharmacokinetics (PK) of levonorgestrel-based
emergency contraception (LNG-EC) in obese and normal body mass index (BMI) users and
test whether doubling the dose of LNG-EC in obese women increases total and free (active)
LNG serum concentrations.
Study design
Healthy, reproductive-age women with obese and normal BMIs received 1.5 mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also
received 3 mg LNG (ECx2). Dosing occurred during the follicular phase. Total and free LNG PK
parameters were obtained via serum samples through an indwelling catheter at 0, 0.5,
1, 1.5, 2, and 2.5 h. The primary outcome was the difference in total and free LNG concentration maximum
(Cmax) between ECx1 and ECx2 in the obese group.
Results
A total of 10 women enrolled and completed the study (normal BMI=5, median 22.8 kg/m2, range 20.8–23.7; obese BMI=5, 39.5 kg/m2, range 35.9–46.7). The total LNG Cmax for obese subjects following ECx1 (5.57±2.48 ng/mL) was significantly lower than the level observed in normal BMI women (10.30±2.47, p=.027). Notably, ECx2 increased the Cmax significantly (10.52±2.76, p=.002); approximating the level in normal BMI subjects receiving ECx1. Free LNG Cmax
followed a similar pattern.
Conclusion
Obesity adversely impacts both the total and free Cmax levels of LNG EC and this likely
explains its lack of efficacy in obese women. Doubling the dose appears to correct
the obesity-related PK changes but additional research is needed to determine if this
also improves EC effectiveness in obese women.
Implications
This study demonstrates that obesity interferes with the pharmacokinetics of LNG EC,
and that doubling the dose may be an effective strategy to improve its efficacy in
obese women.
Keywords
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Article info
Publication history
Published online: March 19, 2016
Accepted:
March 13,
2016
Received in revised form:
March 2,
2016
Received:
November 2,
2015
Footnotes
☆Clinical trials#: NCT02408692.
☆☆Authors Disclosures: A. Edelman: consultant for World Health Organization, Gynuity Health Projects, Genzyme, and Agile Therapuetics. Nexplanon trainer for Merck. Author for UptoDate (Royalties received). J. Jensen has received payments for consulting from Agile Pharmaceuticals, Abbvie Pharmaceuticals, Bayer Healthcare, ContraMed, Evofem Inc., HRA Pharma, Merck Pharmaceuticals, Microchips, Teva Pharmaceuticals and the Population Council. He has also received research funding from Abbvie, Bayer, Merck, FHI360, Medicines 360, the Population Council, and the Bill & Melinda Gates Foundation. These companies and organizations may have a commercial or financial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by OHSU. G. Cherala, S Blue, and D Erikson have nothing to disclose.
★Financial Support: Support for this research was from Medical Research Foundation of Oregon (Grant #1501) as well as grant support from National Institutes of Health the OHSU Oregon Clinical & Translational Research Institute (NIH NCRR 1 UL1 RR024120).
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© 2016 Elsevier Inc. All rights reserved.
