Tacrolimus in corticosteroid-resistant ulcerative colitis

Abstract

We report a case of refractory ulcerative colitis treated with tacrolimus. The patient was a 73-year-old woman with a 45-year history of ulcerative colitis. An attack unresponsive to intravenous corticosteroid therapy occurred when she was age 73. Leukocytapheresis therapy was attempted, but was discontinued because of the patient's poor general condition. Cyclosporine A therapy brought about fair control of the disease. A liver injury that was suspected to be associated with this agent, however, occurred within 5 weeks of its initiation. At that time, the cyclosporine A was discontinued and azathioprine treatment was started. Within 6 weeks, signs of exacerbation of the ulcerative colitis became apparent. Tacrolimus administered at that time brought about remission of the disease, and the corticosteroid dose was then reduced. Tacrolimus, like cyclosporine A, appears to be effective for the treatment of attacks of ulcerative colitis.

The effect of tacrolimus (FK-506) on Japanese patients with refractory Crohn’s disease

“…Since the fi rst suggestion that tacrolimus might be used to treat liver transplant recipients with IBD, 13 several case reports and uncontrolled trials have demonstrated the effi cacy of tacrolimus treatment in patients with CD and ulcerative colitis (UC). 8,11,[14][15][16][17] Our study is the fi rst to explore the effi cacy and safety of tacrolimus treatment in Japanese patients with CD and confi rms previous reports in other populations.…”

Nanoparticles Enhance Therapeutic Efficiency by Selectively Increased Local Drug Dose in Experimental Colitis in Rats

“…Standard drug formulations applied in the clinical studies with FK506 (Fellermann et al, 1998;Matsuhashi et al, 2000) released the drug during the intestinal passage followed by its systemic absorption. After oral administration, the effective dose of FK506 is lowered distinctly due to drug's P-gp-related efflux combined with inactivation from mucosal metabolism by CYP3A, which cause a relatively low bioavailability (Kagayama et al, 1993;Shimomura et al, 2002), subsequently reducing the therapeutic efficiency.…”

“…Therefore, low-molecular weight immune-suppressant drugs may still be of interest, however, requiring the design of intelligent drug delivery systems providing a more local treatment. FK506 (tacrolimus), initially developed as an immune-suppressive drug used to inhibit transplantation rejection, was successfully applied in IBD to treat refractory ulcerative colitis where corticoid treatment failed (Hoshino et al, 1995;Aiko et al, 1997;Fellermann et al, 1998;Matsuhashi et al, 2000). These treatments were based on oral FK506 administration with macroscopic carriers (tablets, etc.)…”

Conventional Medical Management of Ulcerative Colitis: Tacrolimus

“…Encouraged by positive effects of tacrolimus in sclerosing cholangitis (PSC) liver transplant recipients on their associated ulcerative colitis [ 19,20 ] anecdotal reports and case series of its use in autoimmune enteropathy [ 21 ] and inflammatory bowel disease followed [22][23][24][25][26] .…”