OBJECTIVE To investigate the pharmacokinetics and pharmacodynamics of oral colon-targeted formulations of tofacitinib(TOF) in rats.

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

RESULTS Compared with the regular TOF formulation, the oral colon-targeted formulation reduced systemic plasma exposure while increasing colonic drug concentration at the same daily dose the administration frequency was also optimized from twice a day to once a day. Moreover, the oral colon-targeted formulation demonstrated comparable or superior improvements in colonic gross morphology, disease activity index scores, histopathological lesions, and inflammatory markers in UC rats.

CONCLUSION Compared with the regular TOF formulation, the TOF oral colon-targeted formulation exhibited significant colonic targeting characteristics in the rat body after the same daily dose administration. The oral colon-targeted formulation was comparable or even superior in improving OXA-induced colitis in rats. Moreover, the administration frequency was optimized from twice a day to once a day, which greatly improved the administration compliance for the long-term treatment of UC.