OBJECTIVE To conduct pharmacokinetic and pharmacodynamic investigations of oral colon-targeted tofacitinib(TOF) formulations in rats.

METHODS Plasma concentration profiles and colonic tissue distribution of TOF between the regular TOF formulation and the oral colon-targeted TOF formulation were compared in rats. An oxazolone-induced rat model of ulcerative colitis(UC) was established. The therapeutic efficacy of the oral colon-targeted TOF formulation on UC was assessed based on disease activity index, colon length-to-weight ratio, gross colonic morphology, colonic pathological score and colonic inflammatory cytokines in rats.

RESULTS Compared with the regular TOF formulation at the same daily dosage, the oral colon-targeted TOF formulations reduced systemic plasma drug exposure and elevated colonic drug exposure. Meanwhile, the administration regimen was optimized from twice daily to once daily, with equivalent or superior improvements in gross colonic morphology, disease activity index score, colonic histopathological lesions and colonic inflammatory cytokines in UC rats.

CONCLUSION  The oral colon-targeted TOF formulation demonstrate effective colon-targeting properties and enabled once-daily administration while maintaining or improving anti-inflammatory efficacy, providing a more clinically valuable therapeutic strategy for the long-term treatment of UC.