title: Pharmacokinetics of levonorgestrel and ulipristal acetate emergency contraception in women with normal and obese body mass index.
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.
  
  
  METHODS
  This prospective, randomized crossover study evaluates the PK of women after single doses of LNG-EC (1.5mg) and UPA-EC (30mg). 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 48h). 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 AUC0-24and maximum concentration (Cmax) were 50% lower among obese-BMI women than among normal-BMI women (AUC0-24100.8 vs. 208.5ng*h/mL, IQRobese-BMI35.8, IQRnormal-BMI74.2, p≤.01; Cmax10.8 vs. 18.2ng/mL, p=.01). After UPA-EC, AUC0-24and Cmaxwere similar between obese-BMI and normal-BMI women (AUC0-24362.5 vs. 293.5ng*h/mL, IQRobese-BMI263.2, IQRnormal-BMI112.5, p=.15; Cmax95.6 vs. 89.3ng/mL, p=.70).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University Medical Center, PH 16-69, 622 West 168th Street, New York, NY 10032, United States. Electronic address: piyapa.praditpan@nyumc.org.
authors.forename: Piyapa
authors.initials: P
authors.lastname: Praditpan
authors.affiliation: Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, United States.
authors.forename: Angie
authors.initials: A
authors.lastname: Hamouie
authors.affiliation: Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, United States.
authors.forename: Cale N
authors.initials: CN
authors.lastname: Basaraba
authors.affiliation: Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY 10032, United States.
authors.forename: Renu
authors.initials: R
authors.lastname: Nandakumar
authors.affiliation: Department of Pathology and Cell Biology, Department of Medicine and Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY 10032, United States.
authors.forename: Serge
authors.initials: S
authors.lastname: Cremers
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University Medical Center, PH 16-69, 622 West 168th Street, New York, NY 10032, United States.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Davis
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University Medical Center, PH 16-69, 622 West 168th Street, New York, NY 10032, United States; Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, United States.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Westhoff
mesh_terms: D000328:Adult; D015992:Body Mass Index; D003281:Contraceptives, Postcoital / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000493:pharmacokinetics*; D008875:Middle Aged; D009649:Norpregnadienes / Q000493:pharmacokinetics*; D009765:Obesity / Q000097:blood*; D011446:Prospective Studies
chemical_list: D003281:Contraceptives, Postcoital; D009649:Norpregnadienes; D016912:Levonorgestrel; C555622:ulipristal acetate
keywords: Emergency contraception; Levonorgestrel; Obesity; Pharmacokinetics; Ulipristal acetate