PHARMACOKINETICS OF NICOTINE TARTRATE AFTER SINGLE-DOSE LIQUID ENEMA,ORAL, AND INTRAVENOUS ADMINISTRATION

Ulcerative colitis is predominantly a disease of nonsmokers, and trans dermal nicotine is therapeutic but often results in adverse reactions. Colonic administration of nicotine tartrate as a liquid enema could d ecrease systemic nicotine absorption and adverse reactions. The purpos e of the current study was to determine the bioavailability and pharma cokinetic parameters of nicotine after administration by hydrophilic l iquid enema (acidic and basic), hydrophobic liquid enema (acidic and b asic), and by oral and intravenous routes. Thirty healthy volunteers r eceived 45 mu g nicotine base/kg (as nicotine tartrate) in one of five formulations (each n = 6): hydrophilic acidic liquid enema, hydrophil ic basic liquid enema, hydrophobic acidic liquid enema, hydrophobic ba sic liquid enema, and oral solution. All participants also received 15 mu g nicotine base/kg (as nicotine tartrate) intravenously during a s eparate study period. Serum concentrations of nicotine were determined by gas chromatography with mass spectrometry. The mean (+/- SD) bioav ailabilities of nicotine after administration in the liquid enema form ulations (hydrophilic acidic 17 +/- 18%, hydrophilic basic 16 +/- 16%, hydrophobic acidic 25 +/- 17%, hydrophobic basic 15 +/- 12%) were sim ilar to the bioavailability of nicotine after administration by oral s olution (20 +/- 25%). The bioavailabilities of nicotine for all five n onintravenous formulations were significantly less than for intravenou s nicotine (100%). Serum concentrations of nicotine did not predict ad verse reactions. Nicotine tartrate administered as either a liquid ene ma or as an oral solution had low bioavailability and was well tolerat ed. The therapeutic potential of nicotine tartrate liquid enemas, whic h can potentially limit toxicity by local (colonic) delivery of high d oses of nicotine should be investigated in patients with left-sided ul cerative colitis.