title: Evaluation of the Effect of Tofacitinib on the Pharmacokinetics of Oral Contraceptive Steroids in Healthy Female Volunteers.
abstract: Tofacitinib is an oral Janus kinase inhibitor. Tofacitinib metabolism is primarily mediated by cytochrome P450 3A4. This phase 1 randomized, open-label, 2-way crossover study (NCT01137708) evaluated the effect of tofacitinib 30 mg twice daily 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 women. 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 coadministered with tofacitinib. The 90% confidence intervals for the adjusted geometric mean ratios for AUC∞ fell within the 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, for EE; 25.9 and 25.4 hours, respectively, for 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 coadministered with tofacitinib.
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Menon
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Riese
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Wang
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Christine W
authors.initials: CW
authors.lastname: Alvey
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Haihong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Pfizer Clinical Research Unit, Brussels, Belgium.
authors.forename: Wendy
authors.initials: W
authors.lastname: Petit
authors.affiliation: Pfizer Inc, Groton, CT, USA. sriram.krishnaswami@pfizer.com.
authors.forename: Sriram
authors.initials: S
authors.lastname: Krishnaswami
mesh_terms: D000328:Adult; D019540:Area Under Curve; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004338:Drug Combinations; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; C479163:tofacitinib; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: drug-drug interactions; ethinylestradiol; levonorgestrel; oral contraceptives; tofacitinib