Piyapa Praditpan1, Angie Hamouie2, Cale N Basaraba2, Renu Nandakumar3, Serge Cremers4, Anne R Davis5, Carolyn L Westhoff6. 1. 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. 2. Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, United States. 3. Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY 10032, United States. 4. 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. 5. Department of Obstetrics and Gynecology, Columbia University Medical Center, PH 16-69, 622 West 168th Street, New York, NY 10032, United States. 6. 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.
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 (1.5mg) 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 AUC0-24 and maximum concentration (Cmax) were 50% lower among obese-BMI women than among normal-BMI women (AUC0-24 100.8 vs. 208.5ng*h/mL, IQRobese-BMI 35.8, IQRnormal-BMI 74.2, p≤.01; Cmax 10.8 vs. 18.2ng/mL, p=.01). After UPA-EC, AUC0-24 and Cmax were similar between obese-BMI and normal-BMI women (AUC0-24 362.5 vs. 293.5ng*h/mL, IQRobese-BMI 263.2, IQRnormal-BMI 112.5, p=.15; Cmax 95.6 vs. 89.3ng/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.
RCT Entities:
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-BMIwomen. STUDY DESIGN: 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-BMIparticipants, 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-BMIwomen than among normal-BMI women (AUC0-24 100.8 vs. 208.5ng*h/mL, IQRobese-BMI 35.8, IQRnormal-BMI 74.2, p≤.01; Cmax 10.8 vs. 18.2ng/mL, p=.01). After UPA-EC, AUC0-24 and Cmax were similar between obese-BMI and normal-BMI women (AUC0-24 362.5 vs. 293.5ng*h/mL, IQRobese-BMI 263.2, IQRnormal-BMI 112.5, p=.15; Cmax 95.6 vs. 89.3ng/mL, p=.70). CONCLUSION: After a single dose of EC, obese-BMIwomen 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-BMIwomen, 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: Alison B Edelman; Jon D Hennebold; Kise Bond; Jeong Y Lim; Ganesh Cherala; David F Archer; Jeffrey T Jensen Journal: Obstet Gynecol Date: 2022-06-07 Impact factor: 7.623
Authors: Carolyn L Westhoff; Hua Guo; Zhong Wang; Hanina Hibshoosh; Margaret Polaneczky; Malcolm C Pike; Richard Ha Journal: Breast Cancer Res Treat Date: 2022-01-11 Impact factor: 4.624
Authors: Melissa Natavio; Frank Z Stanczyk; Emilie A G Molins; Anita Nelson; William J Jusko Journal: Contraception Date: 2019-01-28 Impact factor: 3.051