Peak plasma levels of nicotine occur 2–10 min after smoking tobacco. Nicotine undergoes a large first-pass effect during which the liver metabolizes 80–90%. Protein binding ranges from 4.9% to 20%. The apparent volume of distribution varies between 1 and 3 l/kg. The metabolites include isomethylnicotinium ion, nornicotine, cotinine, and nicotine-1-N-oxide. Nicotine passes into breast milk in small quantities. In addition to nicotine, tobacco smoke contains small amounts of the alkaloids anatabine, anabasine, nornicotine, N-methylanabasine, anabaseine, nicotine N'-oxide, myosmine, β-nicotyrine, cotinine, and 2,3'-bipyridyl.