Extended-release once-daily formulation of tofacitinib: evaluation of pharmacokinetics compared with immediate-release tofacitinib and impact of food

J Clin Pharmacol. 2016 Mar 11. doi: 10.1002/jcph.734. [Epub ahead of print]

PK profile of TOF is rapid absorption and elimination with time to max concentration 0.5-1 hour and terminal half-life at 3 hours. It is currently approved for immediate release (IR) 5 mg BID, 10 mg total; however, decreasing the dosage to QD dosing may help increase compliance. This study performed in 24 healthy males compared the PK of XR and IR TOF under both single and multiple dose conditions and evaluated the effect of a high-fat meal on the PK of XR TOF. There were no clinically important adverse events observed during this study. Although the Cmax was reached later for XR 11 mg than for IR 5 mg dose, the numerical value was similar between the two formulations. Minimum plasma concentrations, as measured by Cmin and Ctrough were approximately 29% and 26% lower, respectively, for the XR formulation. Cmax was increased in the groups fed a high-fat meal, given the similar AUC values, was not considered significant. This study showed the XR TOF has similar bioavailability to IR TOF, as total and peak exposures that were equivalent between XR and IR TOF, as measured by AUC and Cmax.