Evaluation of tofacitinib citrate bioequivalence based on pharmacokinetic parameters in healthy Chinese subjects

Objective To evaluate the pharmacokinetics and bioequivalence of tofacitinib citrate using pharmacokinetic parameters, a single-dose, randomized-sequence, two-way crossover study of tofacitinib citrate test (T) and reference (R) formulations, with a 4-day washout period, was performed. Materials and methods 72 healthy Chinese subjects were randomly divided into 4 groups: sequence A (TR) and B (RT) in a fasted state and sequence C (TR) and D (RT) in a fed state. Plasma tofacitinib citrate levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the pharmacokinetic parameter maximum concentration (Cmax) and area under the concentration-time curve (AUC0-t and AUC0-∞) were used to evaluate bioequivalence. Results The geometric least-squares mean (GLSM) ratio and 90% confidence intervals for fasted state Cmax, AUC0-t, and AUC0-∞ were 93.90 - 108.17%, 100.41 - 103.95%, and 100.48 - 104.02% and at fed state were 99.45 - 119.52%, 100.05 - 104.23%, and 100.00 - 104.20%, respectively. The 90% CI of the two preparations, Cmax, AUC0-t, and AUC0-∞, all fell within the equivalent range of 80 - 125%. tmax was ~ 0.6 hours later, and Cmax was ~ 27% lower after a high-fat diet in the fasted state. Conclusion Two types of tofacitinib citrate tablets were bioequivalent under both fasted and fed conditions, and both were generally well tolerated; moreover, food-drug interaction may affect drug pharmacokinetics.