Low-dose oral microemulsion ciclosporin for severe, refractory ulcerative colitis

Aliment Pharmacol Ther. 2005 Aug 1;22(3):203-8. doi: 10.1111/j.1365-2036.2005.02552.x.

Abstract

Background: The optimal modalities of treatment with oral microemulsion ciclosporin in patients with severe, steroid-refractory ulcerative colitis are uncertain.

Aim: To assess the applicability, in terms of efficacy and tolerability, of a standard oral microemulsion ciclosporin treatment protocol targeting relatively low blood ciclosporin concentrations, in patients with severe, steroid-resistant ulcerative colitis.

Patients and methods: Patients with a severe attack of ulcerative colitis and no satisfactory response to intravenous corticosteroids were started on oral microemulsion ciclosporin. Dosages were adapted according to a standard protocol, targeting a blood predose ciclosporin concentration (C0) of 100-200 ng/mL. Patients without a clinical response on day 8 were scheduled for colectomy.

Results: Sixteen patients were enrolled. A clinical response was observed in 14/16 (88%). The mean clinical activity index scores and concentrations of C-reactive protein on days 0, 4 and 8 were 11.8, 6.7 and 4.1, and 50.3, 19.3 and 9.7 mg/L respectively. The mean C0 (days 0-8) was 149 pg/mL. The mean creatinine clearance rates on days 0 and 8 were 88 and 96 mL/min. One patient had an acute elevation of transaminases that resulted in discontinuing ciclosporin.

Conclusions: Even when dosed for a target C0 of 100-200 ng/mL, oral microemulsion ciclosporin for severe, steroid-refractory ulcerative colitis achieves an efficacy similar to that attained with higher, potentially more toxic levels. The oral route should replace intravenous treatment in this clinical setting.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • C-Reactive Protein / metabolism
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / drug therapy*
  • Cyclosporine / administration & dosage*
  • Cyclosporine / blood
  • Cyclosporine / therapeutic use
  • Drug Administration Schedule
  • Emulsions
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / therapeutic use
  • Microchemistry
  • Middle Aged
  • Severity of Illness Index
  • Treatment Failure

Substances

  • Adrenal Cortex Hormones
  • Emulsions
  • Immunosuppressive Agents
  • Cyclosporine
  • C-Reactive Protein