Pharmacokinetics of levonorgestrel and ulipristal acetate emergency contraception in women with normal and obese body mass index

• Published in: Contraception (Stoneham) Vol. 95; no. 5; pp. 464 - 469
• Main Authors: Praditpan, Piyapa, Hamouie, Angie, Basaraba, Cale N, Nandakumar, Renu, Cremers, Serge, Davis, Anne R, Westhoff, Carolyn L
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2017
• Subjects: Adult; Body Mass Index; Contraceptives, Postcoital - pharmacokinetics; Cross-Over Studies; Emergency contraception; Female; Humans; Levonorgestrel; Levonorgestrel - pharmacokinetics; Middle Aged; Norpregnadienes - pharmacokinetics; Obesity; Obesity - blood; Obstetrics and Gynecology; Pharmacokinetics; Prospective Studies; Ulipristal acetate; Obesity; Pharmacokinetics; Emergency contraception; Levonorgestrel; Ulipristal acetate
• ISSN: 0010-7824; 1879-0518
• DOI: 10.1016/j.contraception.2017.01.004

Abstract Objective This study compares the pharmacokinetics (PK) of levonorgestrel (LNG) emergency contraceptive (EC) and ulipristal acetate (UPA)-EC between normal-body mass index (BMI) and obese-BMI women. Study design This prospective, randomized crossover study evaluates the PK of 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-h admissions. Study staff collected 14 blood specimens (0, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 48 h). We evaluated serum concentrations of LNG and UPA using liquid chromatography–tandem mass spectroscopy and estimated the PK parameters of both drugs using noncompartmental analysis. The main outcome of this study was a comparison of between-group differences in AUC0–24. Results Thirty-two women completed the study (16 in each group). Among normal-BMI and obese-BMI participants, the mean BMIs were 22.0 (range 18.8–24.6) and 34.3 (range 30.6–39.9), respectively. After LNG-EC, mean AUC0–24 and maximum concentration ( Cmax ) were 50% lower among obese-BMI women than among normal-BMI women (AUC0–24 100.8 vs. 208.5 ng*h/mL, IQRobese-BMI 35.8, IQRnormal-BMI 74.2, p≤.01; Cmax 10.8 vs. 18.2 ng/mL, p=.01). After UPA-EC, AUC0–24 and Cmax were similar between obese-BMI and normal-BMI women (AUC0–24 362.5 vs. 293.5 ng*h/mL, IQRobese-BMI 263.2, IQRnormal-BMI 112.5, p=.15; Cmax 95.6 vs. 89.3 ng/mL, p=.70). Conclusion After a single dose of EC, obese-BMI women are exposed to lower concentrations of LNG and similar concentrations of UPA, when compared to normal-BMI women. Implications Differences in LNG-EC PK by BMI group may underlie and account for the lower LNG-EC efficacy reported among obese-BMI women, but modest differences in UPA-EC PK by BMI group provide less support for variable efficacy. A pharmacodynamic study may be able to clarify whether these PK differences account for observed differences in LNG-EC and UPA-EC efficacy.