Protracted elimination of cocaine metabolites in long-term, high-dose cocaine abusers

Abstract

M ounting public concern about cocaine abuse has led to increased urine testing in drug treatment programs and in the workplace. Since cocaine is rapidly eliminated from plasma, urine tests for cocaine generally detect its principal metabolite, benzoylecgonine, rather than cocaine itself; cocaine is metabolized primarily to benzoylecgonine and ecgonine-methyl-ester by plasma esterases [1]. The elimination half-lives of both cocaine and benzoylecgonine have been well documented, with reported ranges of approximately 20 to 90 minutes for cocaine [2-4], and six to eight hours for benzoylecgonine [5]; the limit of detectability for benzoylecgonine has been estimated to be 60 hours after cocaine use [1]. This limit has resulted in a clinical axiom that the presence of benzoylecgonine in a person's urine proves that cocaine use has occurred within the past two to three days [6,7]. Consequently, continued detection beyond this time may have substantial personal or treatment implications. For example, continued abuse of cocaine after entering treatment may be grounds for forced discharge from many inpatient drug treatment facilities and outpatient methadone maintenance programs. Moreover, employees often receive warnings after initial detection of drug use; evidence of subsequent use may result in termination of employment. However, there are important but little recognized restrictions to clinical generalizations from the cited kinetic studies of cocaine disposition [1-5]. First, the data reported in these studies are derived from shortterm, single-dose studies rather than after repeated doses or during long-term cocaine administration. Second, doses administered in these studies were low compared with street doses used by many cocainedependent individuals. Third, the subjects generally lacked substantial histories of cocaine or other substance abuse. Consequently, these kinetic studies may not accurately reflect the disposition or metabolism of cocaine after extraordinarily high recent doses or massive total exposure. Some authors have suggested that cocaine disposition or metabolism may vary with the amount or frequency of drug intake [4,8]. However, clinical examples supporting this hypothesis have not yet been cited. We report herein on three cases of veryhigh-dose cocaine abuse, in which benzoylecgonine continued to be detected for 10 to 22 days after cessation of cocaine intake.