Disposition of nicotine in the rat after intravenous administration

The pharmacokinetics of 14C-labeled nicotine were studied in male Fischer-344 rats following the i.v. administration of a single 0.8 mg/kg dose. Serial blood samples were collected and the nicotine in plasma was separated from its metabolites by TLC. The levels of radioactivity corresponding to nicotine, cotinine, and polar metabolites remaining at the origin of the chromatogram were determined by liquid scintillation counting. Plasma nicotine concentration was characterized by a biexponential decay with a mean biologic half-life (t1/2) of 0.96 hrs, a large apparent volume of distribution (5.67 L/kg) and total body clearance (4.04 L/hr/kg). Maximum plasma concentration of cotinine was reached within 1 1/2 hrs post-nicotine administration, followed by a monoexponential decline with a mean t1/2 of 6.4 hrs. The plasma concentrations of origin activity rose to maximum levels within 30 minutes and declined slowly in a biexponential fashion with a mean t1/2 of 23.2 hrs. It appears, therefore, that while nicotine is rapidly eliminated, its metabolites persist in the plasma a long time after its administration.