title: A comparison of the pharmacokinetic profile of an ascending-dose, extended-regimen combined oral contraceptive to those of other extended regimens.
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.
authors.affiliation: Clinical Pharmacology, SCI-MED BRIDGE, Malvern, PA, USA.
authors.forename: Mona
authors.initials: M
authors.lastname: Darwish
authors.affiliation: Phase 1 & Clinical Pharmacology, Teva Branded Pharmaceutical Products, R&D, Inc., Frazer, PA, USA mary.bond@tevapharm.com.
authors.forename: Mary
authors.initials: M
authors.lastname: Bond
authors.affiliation: Teva Women's Health, Teva Branded Pharmaceutical Products, R&D, Inc., Frazer, PA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Ricciotti
authors.affiliation: Global Biostatistics, Teva Branded Pharmaceutical Products, R&D, Inc., West Chester, PA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hsieh
authors.affiliation: Pharmacometric Services, Cognigen Corporation, Buffalo, NY, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Fiedler-Kelly
authors.affiliation: Pharmacometric Services, Cognigen Corporation, Buffalo, NY, USA.
authors.forename: Thaddeus
authors.initials: T
authors.lastname: Grasela
mesh_terms: D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D003198:Computer Simulation; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019304:Ethinyl Estradiol-Norgestrel Combination / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D008954:Models, Biological; D017711:Nonlinear Dynamics; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D004338:Drug Combinations; C482584:Seasonale; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D019304:Ethinyl Estradiol-Norgestrel Combination
keywords: ascending-dose; bleeding; combined oral contraceptive; ethinyl estradiol; extended regimen