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.

AIM:

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: W J Sandborn, W J Tremaine, J A Leighton, G M Lawson, B J Zins, R F Compton, D C Mays, J J Lipsky, K P Batts, K P Offord, R D Hurt, J Green
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 11 Issue 4 Pg. 663-71 (Aug 1997) ISSN: 0269-2813 [Print] England
• PMID: 9305473 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Nicotinic Agonists
• Nicotine
• Cotinine

Topics

• Adult
• Aged
• Colitis, Ulcerative (blood, drug therapy)
• Cotinine (blood)
• Diarrhea (chemically induced)
• Dizziness (chemically induced)
• Enema
• Female
• Humans
• Male
• Middle Aged
• Nausea (chemically induced)
• Nicotine (administration & dosage, adverse effects, blood)
• Nicotinic Agonists (administration & dosage, adverse effects, blood)
• Salvage Therapy