Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics and adverse events associated with three doses of nicotine

Aliment Pharmacol Ther. 2004 Oct 15;20(8):859-65. doi: 10.1111/j.1365-2036.2004.02199.x.


Background: Transdermal nicotine is of value in active ulcerative colitis but causes adverse events because of systemic absorption. Nicotine enemas may give rise to fewer adverse events.

Aim: To assess the pharmacokinetics of nicotine enemas in three doses.

Methods: Thirteen volunteers, all non-smokers but three ex-smokers, were given enemas on separate occasions containing 3, 6 and 9 mg of nicotine, in ascending dose order. Adverse events were recorded and blood samples taken over 8 h for measurement of serum nicotine and cotinine.

Results: Enemas were retained by most subjects. Eleven of 14 adverse events were 'early'--30-105 min after the enema, corresponding to maximum plasma nicotine concentrations; three events were later, 4-8 h after the enema and unrelated to the tmax. 'Early' adverse events occurred in eight subjects--six with 9 mg. The three highest plasma nicotine concentrations were with 9 mg and associated with headache, nausea and sweating. Only one had adverse events with 3 mg and withdrew from the study. Nicotine Cmax with 6 and 9 mg doses were respectively two and three times the value with 3 mg. Peak nicotine concentrations occurred 44-50 min after the enema.

Conclusion: The 6 mg dose of nicotine probably represents the dose to use in clinical practice - for the highest therapeutic dose with a low risk of adverse events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Colitis, Ulcerative / drug therapy*
  • Dose-Response Relationship, Drug
  • Enema / methods
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nicotine / administration & dosage*
  • Nicotine / adverse effects
  • Nicotine / pharmacokinetics
  • Nicotinic Agonists / administration & dosage*
  • Nicotinic Agonists / adverse effects
  • Nicotinic Agonists / pharmacokinetics


  • Nicotinic Agonists
  • Nicotine