Cocaine, Ecgonine Methyl Ester, and Benzoylecgonine Plasma Profiles in Rhesus Monkeys

From a public health point of view, cocaine (COC) presents serious clinical problems and deaths from overdose and lifelong addiction patterns, not to mention its involvement in crime, in the United States. This study subjected rhesus monkeys to one intravenous administration of COC (1 mg/kg), which closely imitates the smoking of “crack” COC with regard to dose and effect. We monitored plasma concentrations over time, beginning when the primates were in a state of hyperarousal. Blood was sampled at 1, 6, 12, and 40 min after dosing. Plasma concentrations of COC decreased rapidly with a half life of 15.7 min. Mean COC concentrations in the drug-treated group (n = 7) for the four timepoints were 296, 225, 187, and 80 ng/mL, respectively. Ecgonine methyl ester (EME) concentrations ranged from 57 to 91 ng/mL. When compared with the 1-min COC concentrations, the mean EME concentration was 30.7%. Benzoylecgonine (BZE) ranged from 34 to 42 ng/mL, and the mean concentration was 11.5% of the mean COC concentration at 1 min. EME and BZE concentrations did not vary appreciably over the time course of the study. Plasma norcocaine concentrations were less than the limit of detection of 25 ng/mL. Because a rapid decline in plasma COC concentrations over time was observed along with a very small change in EME and BZE concentrations, we attribute tissue redistribution of COC, particularly to the brain, as significant and metabolism or hydrolysis of COC as minor.