Pharmacokinetics of nicotine carbomer enemas: A new treatment modality for ulcerative colitis

作者：John T. Green, Gareth A.O. Thomas, John B. Rhodes, Brian K. Evans, Michael A. H. Russell, C Feyerabend, Grant S. Fuller, Robert Gordon Newcombe, William J. Sandborn · 发表于：Clinical Pharmacology & Therapeutics · 年份：1997 · DOI：10.1016/s0009-9236(97)90167-3 · 被引用次数：25 · 研究领域：Nicotinic Acetylcholine Receptors Study、Vagus Nerve Stimulation Research、Berberine and alkaloids research

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference...