Evaluation of the Effect of Tofacitinib on the Pharmacokinetics of Oral Contraceptive Steroids in Healthy Female Volunteers.
Level 2 - randomized trial
Randomized open-label crossover pharmacokinetic trial
PubMed 27138968 · doi:10.1002/cpdd.270
What was done
In a phase 1, randomized, open-label, 2-way crossover trial (NCT01137708), 19 healthy female volunteers received a single oral dose of Microgynon 30 (30 µg ethinylestradiol [EE] and 150 µg levonorgestrel [LN]) alone and in combination with tofacitinib 30 mg twice daily. The single-dose pharmacokinetics (AUC∞, maximal plasma concentrations [Cmax], and elimination half-life) of EE and LN were compared between treatments.
What was found
In the presence of tofacitinib, AUC∞ increased by 6.6% for EE and 0.9% for LN, with the 90% confidence intervals for the adjusted geometric mean ratios falling within the 80% to 125% equivalence boundary for both steroids. Cmax decreased by 10.4% for EE and increased by 12.2% for LN. Mean elimination half-life was similar with and without tofacitinib: 13.8 versus 13.3 hours for EE, and 25.9 versus 25.4 hours for LN.
Why it matters
Tofacitinib does not exert clinically meaningful inductive or inhibitory effects on the metabolism of ethinylestradiol or levonorgestrel, indicating dose adjustments are not required when these oral contraceptives are coadministered.
Limits
The study sample was small (19 healthy women) and evaluated only a single-dose contraceptive regimen rather than steady-state use. Findings from healthy volunteers may not capture disease-related pharmacokinetic variability, and clinical contraceptive efficacy (ovulation inhibition) was not directly assessed.
Cited by
- supports The combination birth control pill has a biological half-life of 28 hours.