TO THE EDITOR:
I read with interest the report by Sandborn and colleagues [1] on the efficacy of transdermal nicotine for mildly to moderately active ulcerative colitis. They reported that the highest tolerated dosage of nicotine improved clinical activity but did not induce histologic remission.
I am of the opinion that chronic effects by an intensive exposure to nicotine should be carefully assessed before patients received nicotine therapy in clinical practice. Several N-nitrosamines, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are synthesized from nicotine; these carcinogens would increase the risk for cancer [2, 3]. In Sandborn and colleagues' study, the serum levels of nicotine in the patients who received the 22-mg patch consistently exceeded 13 ng/mL. This finding is in agreement with the maximal increment level of nicotine (14.3 ng/mL) seen after patients in another study smoked a cigarette containing 1 mg of nicotine [4]. This would mean that the patients were exposed to as much nicotine as would have been seen had they smoked cigarettes ceaselessly all day long during therapy. To date, patients with such an intensive exposure to nicotine have not been proven safe from an increased risk for cancer.
Current therapy can cause remission in almost 90% of patients with acute ulcerative colitis [5]. Hence, risk for developing cancer is an important factor in determining the long-term prognosis of this disease. I am afraid that the small quality-of-life benefit may not compensate for the latent risk for cancer in patients with such benign disease.
1. Sandborn WJ, Tremaine WJ, Offord KP, Lawson GM, Petersen BT, Batts KP, et al. Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1997; 126:364-71.
2. Hecht SS, Chen CB, Ornaf RM, Jacobs E, Adams JD, Hoffmann D. Reaction of nicotine and sodium nitrite: formation of nitrosamines and fragmentation of the pyrrolidine ring. Journal of Organic Chemistry. 1978; 43:72-6.
3. Amin S, Desai D, Hecht SS, Hoffmann D. Synthesis of tobacco-specific N-nitrosamines and their metabolites and results of related bioassays. Crit Rev Toxicol. 1996; 26:139-47.
4. Benowitz NL, Porchet H, Sheiner L, Jacob P 3d. Nicotine absorption and cardiovascular effects with smokeless tobacco use: comparison with cigarettes and nicotine gum. Clin Pharmacol Ther. 1988; 44:23-8.
5. Glickman RM. Inflammatory bowel disease: ulcerative colitis and Crohn's disease. In: Wilson JD, Braunwald E, Isselbacher KJ, Petersdorf RG, Martin JB, Fauci AS, et al, eds. Harrison's Principles of Internal Medicine. 12th ed. New York: McGraw-Hill; 1991:1268-81.
Top
Author & Article Info
References
Article
