Pharmacokinetics of levonorgestrel and ulipristal acetate emergency contraception in women with normal and obese body mass index
Contraception
Awarded 2015
Complex Family Planning Fellowship Research
Piyapa Praditpan, MD, MPH
Columbia University
$99,950

Levonorgestrel (LNG) and ulipristal acetate (UPA) emergency contraceptive (EC) efficacy trials suggest more EC failure among women with greater body mass index (BMI); this relationship appears much stronger for LNG-EC than for UPA-EC. Differences in systemic exposure by BMI might explain differences in failures. Thus, the primary objective of this study was to compare the pharmacokinetics (PK) of LNG-EC and UPA-EC between normal-BMI and obese-BMI women.
We evaluated women after single doses of LNG-EC (1.5 mg) and UPA-EC (30 mg). Study procedures took place during clinical research unit admissions, where participants received a standardized meal and each study drug, in random order, during two separate 24-hour admissions. Study staff collected fourteen blood specimens (0, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48h). We evaluated serum levels of LNG and UPA using liquid chromatography-tandem mass spectroscopy (LC-MS/MS), and estimated the PK parameters of both drugs using the STATA14 (Stata Corporation, College Station, TX, USA) non-compartmental analysis procedure, pkexamine.
Thirty-two women completed the study (16 in each group). Among normal-BMI and obese-BMI participants the mean BMI’s were 22.0 (range 18.8-24.6) and 34.3 (range 30.6-39.9), respectively. After LNG-EC, mean AUC0-24 and Cmax were 50% lower among obese-BMI women than among normal-BMI women. After UPA-EC, AUC0-24 and Cmax were similar between obese-BMI and normal-BMI women.
Large differences in LNG-EC PK by BMI group may underlie and account for the decrement in LNG-EC efficacy reported among obese-BMI women. Similarities in UPA-EC PK by BMI group provide less support for variable efficacy among normal-BMI and obese-BMI UPA-EC users. A pharmacodynamic study may be able to clarify whether these PK differences account for observed differences in LNG-EC and UPA-EC efficacy.
In the United States one-third of women ages 20-59 are obese and most obese women are Black or Hispanic. These women account for the majority of the country’s unintended pregnancies and so bear a disproportionate burden of poor maternal and neonatal health outcomes. Enhancing EC efficacy among obese women may help to reduce unintended pregnancies in vulnerable populations.

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