Evaluation of the Effect of Tofacitinib on the Pharmacokinetics of Oral Contraceptive Steroids in Healthy Female Volunteers

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Abstract
Tofacitinib is an oral Janus kinase (JAK) inhibitor. Tofacitinib metabolism is primarily mediated by cytochrome P450 (CYP)3A4. This Phase 1, randomized, open-label, two-way crossover study (NCT01137708) evaluated the effect of tofacitinib 30 mg BID on the single-dose pharmacokinetics of combination oral contraceptives ethinylestradiol (EE) and levonorgestrel (LN). EE and LN were administered as a single Microgynon 30® tablet (30 μg EE and 150 μg LN) to 19 healthy females. In the presence of tofacitinib, the area under the curve from time zero to infinity (AUC∞) increased by 6.6% and 0.9% for EE and LN, respectively. Maximal plasma concentrations decreased by 10.4% for EE and increased by 12.2% for LN when co-administered with tofacitinib. The 90% confidence intervals for the adjusted geometric mean ratios for AUC∞ fell within 80-125% region for both EE and LN. Mean half-life was similar in the presence and absence of tofacitinib: 13.8 and 13.3 hours, respectively (EE); 25.9 and 25.4 hours, respectively (LN). Tofacitinib had no clinically relevant net inhibitory or inductive effect on the pharmacokinetics of EE and LN. Therefore, there is no evidence to suggest dose adjustments of oral contraceptive drugs containing EE or LN when co-administered with tofacitinib. This article is protected by copyright. All rights reserved
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  • Pfizer Inc

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