The JAK1 Inhibitor Upadacitinib Has No Effect on the Pharmacokinetics of Levonorgestrel and Ethinylestradiol: A Study in Healthy Female Subjects.
Level 3 - non-randomized controlled study
Phase I open-label fixed-sequence crossover pharmacokinetic study in healthy volunteers
PubMed 30500075 · doi:10.1002/jcph.1350
What was done
In a phase I, single-center, open-label, 2-period crossover study, 22 healthy female subjects received a single oral dose of ethinylestradiol/levonorgestrel (0.03/0.15 mg) alone in period 1, and again on day 12 during a 14-day regimen of 30 mg once-daily extended-release upadacitinib in period 2. Pharmacokinetic parameters (Cmax, AUC from time zero to infinity, and harmonic mean terminal half-life) were compared between the two treatments.
What was found
Ethinylestradiol and levonorgestrel met standard bioequivalence criteria in the presence and absence of upadacitinib. The ratios (90% confidence intervals) for upadacitinib co-administration versus contraceptive alone were: - Ethinylestradiol Cmax: 0.96 (0.89-1.02) - Ethinylestradiol AUC(0-inf): 1.10 (1.04-1.19) - Ethinylestradiol harmonic mean terminal half-life: 7.7 vs 7.0 hours - Levonorgestrel Cmax: 0.96 (0.87-1.06) - Levonorgestrel AUC(0-inf): 0.96 (0.85-1.07) - Levonorgestrel harmonic mean terminal half-life: 37.1 vs 33.1 hours
Why it matters
These results indicate that upadacitinib does not alter the metabolism of ethinylestradiol or levonorgestrel, supporting co-administration without contraceptive dosage adjustments in clinical practice.
Limits
The trial had a small sample size (n = 22) limited to healthy female participants rather than patients with inflammatory disease. It used an open-label, fixed-sequence crossover design and assessed single-dose contraceptive exposure rather than steady-state contraceptive pharmacokinetics or clinical efficacy.
Cited by
- supports The combination birth control pill has a biological half-life of 28 hours.