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A Comparison of the Pharmacokinetic Profile of an Ascending-Dose, Extended-Regimen Combined Oral Contraceptive to Those of Other Extended Regimens

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Abstract

Quartette (levonorgestrel [LNG]/ethinyl estradiol [EE] and EE) is an ascending-dose, extended-regimen combined oral contraceptive (COC) that consists of a constant dose of LNG 150 µg on days 1 to 84 with EE 20 µg on days 1 to 42, 25 µg on days 43 to 63, 30 µg on days 64 to 84, and 10 µg of EE monotherapy on days 85 to 91. A population pharmacokinetic (PK) model for EE was developed using nonlinear mixed-effects modeling to characterize the PK profile of EE administered in Quartette and other extended-regimen LNG/EE COCs. Model-predicted plasma concentration–time profiles demonstrated a stepwise increase in systemic exposure to EE during the first 84 days of the cycle following each EE dose change. Lower concentrations of EE were noted during the final 7-day period of EE 10 µg. Gradual increases in EE seen with Quartette may decrease the incidence of unscheduled bleeding frequently observed during early cycles of extended-regimen COCs.

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Authors and Affiliations

  1. Clinical Pharmacology, SCI-MED BRIDGE, Malvern, PA, USA

    Mona Darwish PhD

  2. Phase 1 & Clinical Pharmacology, Teva Branded Pharmaceutical Products, R&D, Inc., 41 Moores Road, 19355, Frazer, PA, USA

    Mary Bond MS, MBA

  3. Teva Women’s Health, Teva Branded Pharmaceutical Products, R&D, Inc., Frazer, PA, USA

    Nancy Ricciotti MSN

  4. Global Biostatistics, Teva Branded Pharmaceutical Products, R&D, Inc., West Chester, PA, USA

    Jennifer Hsieh MS

  5. Pharmacometric Services, Cognigen Corporation, Buffalo, NY, USA

    Jill Fiedler-Kelly MS & Thaddeus Grasela PharmD, PhD

Authors
  1. Mona Darwish PhD
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  2. Mary Bond MS, MBA
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  3. Nancy Ricciotti MSN
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  4. Jennifer Hsieh MS
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  5. Jill Fiedler-Kelly MS
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  6. Thaddeus Grasela PharmD, PhD
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Corresponding author

Correspondence to Mary Bond MS, MBA.

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Darwish, M., Bond, M., Ricciotti, N. et al. A Comparison of the Pharmacokinetic Profile of an Ascending-Dose, Extended-Regimen Combined Oral Contraceptive to Those of Other Extended Regimens. Reprod. Sci. 21, 1401–1410 (2014). https://doi.org/10.1177/1933719114526472

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  • DOI: https://doi.org/10.1177/1933719114526472

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