title: Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study.
abstract: BACKGROUND
  Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine as a liquid rectal enema results in less systemic nicotine absorption.
  
  
  OBJECTIVE
  To determine the safety and clinical response of nicotine tartrate liquid enemas for active left-side ulcerative colitis in a pilot study.
  
  
  METHODS
  Ten non-smoking patients with mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy were treated in an open protocol with nightly nicotine tartrate liquid enemas at a dose of 3 mg nicotine base for 1 week then 6 mg for 3 weeks. Clinical assessments were determined at baseline and 4 weeks by endoscopy, physician assessment and a patient diary of daily symptoms. Peak and trough serum nicotine and trough plasma cotinine were determined by gas chromatography/mass spectrometry and high performance liquid chromatography, respectively.
  
  
  RESULTS
  After 4 weeks of treatment, 5/7 patients (71%) showed clinical and sigmoidoscopic improvement (per protocol analysis). The other three patients discontinued therapy within 7 days because of inability to retain the liquid enemas. No patients showed histologic improvement. Six of the patients who completed the 4-week study had peak and trough serum nicotine concentration determined, only 1 of 6 patients had a detectable peak nicotine concentration (value 2.3 ng/mL), and all six patients had undetectable trough nicotine concentrations. The mean trough plasma cotinine concentration was 13 +/- 10 ng/mL. Transient and mild adverse events occurred in 4/10 patients (nausea, lightheadedness, tremor, sleep disturbance). Given the low or undetectable serum nicotine concentrations, these adverse events are not likely to be related to the nicotine enemas.
  
  
  CONCLUSIONS
  Nicotine tartrate liquid enemas administrated at a dose of 3 mg nicotine base/day for 1 week and then 6 mg/day for 3 weeks are safe and appear to result in clinical improvement in some patients with mildly to moderately active, left-sided ulcerative colitis unresponsive to first-line therapy. Placebo-controlled trials are warranted to confirm these preliminary findings.
authors.affiliation: Inflammatory Bowel Disease Clinic, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: W J
authors.initials: WJ
authors.lastname: Tremaine
authors.forename: J A
authors.initials: JA
authors.lastname: Leighton
authors.forename: G M
authors.initials: GM
authors.lastname: Lawson
authors.forename: B J
authors.initials: BJ
authors.lastname: Zins
authors.forename: R F
authors.initials: RF
authors.lastname: Compton
authors.forename: D C
authors.initials: DC
authors.lastname: Mays
authors.forename: J J
authors.initials: JJ
authors.lastname: Lipsky
authors.forename: K P
authors.initials: KP
authors.lastname: Batts
authors.forename: K P
authors.initials: KP
authors.lastname: Offord
authors.forename: R D
authors.initials: RD
authors.lastname: Hurt
authors.forename: J
authors.initials: J
authors.lastname: Green
mesh_terms: D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D003367:Cotinine / Q000097:blood; D003967:Diarrhea / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004733:Enema; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009538:Nicotine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016879:Salvage Therapy
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine; D003367:Cotinine