Abstract

The disposition of radiolabeled cocaine in humans has been studied after three routes of administration: iv injection, nasal insufflation (ni, snorting), and smoke inhalation (si). Metabolism, followed by urinary excretion of metabolites, proved to be the major route of elimination in all cases. Hydrolytic products (benzoylecgonine, ecgonine methyl ester) were the major excretion products. Benzoyl ecgonine was generally most prevalent, but after smoking two subjects excreted larger amounts of ecgonine methyl ester and the ratio of the two compounds averaged lower in subjects who smoked cocaine. Low binding of cocaine to plasma proteins was observed and blood to plasma ratios were essentially unity. The volume of distribution of cocaine is low (2.70 liter/kg for V beta). Absorption of smoked cocaine was rapid (half-time of 1.1 min). Absorption after ni was slower (half-time of 11.7 min). After iv injection, a rapid distribution phase was observed (half-life of 11 min) and the elimination half-life was 78 min. In 16 subjects divided into three groups based on routes, the half-life based on the average rate constant was 69 min. Bioavailability was good after ni (80%). Undecomposed cocaine from si was well absorbed, but observed bioavailability was diminished by degradation from heating.