Different pharmacokinetics of nicotine following intravenous administration of nicotine base and nicotine hydrogen tartarate in rats

Pharmacokinetics of nicotine was studied in rats following intravenous (i.v.) administration of nicotine base (NB) and nicotine hydrogen tartarate salt (NS) at a nicotine dose of 1 mg/kg. The area under the plasma concentration-time curve (AUC), mean residence time (MRT), systemic clearance (CL), distribution volume at steady state (V-ss) and terminal plasma half-life (T-1/2,T-beta) of nicotine were compared between NB and NS. Compared to NS, NB exhibited higher and sustained plasma nicotine levels, thereby yielding significantly (P<0.05) larger AUC (66.3 vs. 27.7 μg ml/min), MRT (165.7 vs. 58.3 min), T-1/2,T-β (144.2 vs. 51.4 min) and a lower CL (18.3 vs. 46.3 ml/min per kg). The V-ss was comparable between the two compounds. The metabolic conversion to cotinine front NS was threefold larger than that from NB. The plasma protein binding and distribution to blood cells were comparable between the compounds. The apparent partition coefficient (APC) of NS decreased as a function of its concentration, while that of NB remained nearly constant. Particles of different mean sizes were observed for the 1% (w/v) aqueous solutions of NS (388.6 nm) and NB (123.8 nm). Different metabolism and/or elimination between NB and NS appear to be mainly responsible for their different pharmacokinetics. (C) 2001 Elsevier Science B.V. All rights reserved.