Cocaine and Benzoylecgonine Excretion in Humans

Abstract Cocaine is rapidly and extensively metabolized. Studies with 3H-labeled cocaine have demonstrated that the drug is biotransformed to at least ten metabolites in the rat, with the concentration of unchanged cocaine in the urine being less than 10% that of the metabolite benzoylecgonine 1. Information on the metabolism and excretion of cocaine in man is limited. Montesinos 2 has reviewed investigations performed in the 1950s and 1960s on chewers of coca leaf. However, these studies not only used analytical methods less specific and sensitive than those available today, but also employed routes of administration different from those currently used for therapy 3 or abuse. Although several recent investigations have demonstrated that cocaine is extensively metabolized to benzoylecgonine in man 4,5 and that plasma cocaine levels diminish rapidly 6, knowledge concerning the extent and rate of metabolism and excretion of parent drug and metabolite is almost nonexistent. Wallace et al 7 measured the urinary excretion of cocaine and benzoylecgonine in ten patients who had been administered cocaine hydrochloride prior to rhinoplastic surgery. These studies were limited to the initial 24 h after drug administration and consisted of three consecutive 8-h collective specimens per patient. It was observed that the excretion of cocaine and benzoylecgonine diminishes rapidly, that benzoylecgonine concentrations in urine consistently exceeded the corresponding cocaine concentrations by a significant amount, and that the benzoylecgonine/cocaine ratios of urine concentrations varied significantly, demonstrating the impracticability of attempting to predict cocaine concentrations from benzoylecgonine data, or conversely.