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.

Cocaine Increases the Intracellular Calcium Concentration in Brain Independently of Its Cerebrovascular Effects

“…In humans, the half-life of benzoylecgonine is known to be longer than in rats (Dempsey et al, 1999) and can be detected in the urine for Ͼ96 h (Hamilton et al, 1977). Like cocaine, benzoylecgonine passes the blood-brain barrier (Spiehler and Reed, 1985), and both compounds can constrict cerebral arteries (Madden and Powers, 1990).…”

Cocaine and metabolites in waste and surface water across Belgium

“…Since it takes approximately 24 h for water to run from the domestic site to a WWTP (personal communication, Alain Vandelannoote, Aquafin), it means that the cocaine abuse on Friday is detected in the samples collected on Saturday. After intake, COC can be measured in urine up to 6 h, while BE is excreted over a larger period (up to 96 h) (Hamilton et al, 1977;Jufer et al, 2000). Therefore, samples from Sunday would still contain traces of BE originating from cocaine abuse on Friday.…”

“…Only a small fraction of COC is excreted in urine as parent compound, while the largest amount is excreted as BE, the most important metabolite, and EME (Ambre et al, 1984(Ambre et al, , 1988. In urine, COC can be detected for approximately 8 h, while BE and EME can be positively identified for more than 96 h (Hamilton et al, 1977;Jufer et al, 2000).…”

Cocaine and Metabolites Urinary Excretion after Controlled Smoked Administration*

“…Three decades ago, Hamilton et al (5) studied urinary excretion in six subjects who insufflated 1.5 mg/kg cocaine hydrochloride (105 mg for a 70 kg person). Peak urine cocaine concentrations of 300 to 24,000 ng/mL were reached in less than 1 h. Peak urine benzoylecgonine (BE) concentrations ranged from 8100 to 70,800 ng/mL with a time to reach maximum concentrations (T max ) of 4 to 8 h. Ambre et al (6) later examined urine from five subjects following 4 h of intravenous infusion of cocaine hydrochloride with total doses ranging from 253 to 700 mg. As expected, peak cocaine and BE concentrations were higher than those of lower single doses, and interestingly, peak ecgonine methyl ester (EME) concentrations often exceeded those of BE.…”