Metabolism
- Cocaine is rapidly metabolized by enzymatic hydrolysis to benzoylecgonine (R-CO-CH3 + H2O → R-CO-OH + R'-OH) and ecgonine methyl ester (R-OCO-R + H2O → R-OH + R'-OH).
- Both metabolites are inactive.
- The enzymes carboxyl esterase (CES2) and butyrylcholine esterase catalyze the reactions in both pathways.
- A third very minor metabolite is produced by demethylation (R-N-CH3 → R-N-H) by CYP3A4 to norcocaine. Although this metabolite is produced in small concentrations, it is both active and neurotoxic.
Cocaine is rapidly cleared from plasma; only about 1-5% of a cocaine dose is excreted unchanged in urine. Benzoylecgonine and ecgonine methyl ester account for about 45% of a dose. The half-life of cocaine varies from 45 minutes to 90 minutes. Benzoylecgonine has a half-life of approximately six to eight hours and can be detected in the urine for one to three days. Ecgonine methyl ester's half-life is around three to eight hours.
