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Understanding cocaine and metabolites urinary excretion following smoking is important for interpretation of urine test results in judicial, workplace and treatment settings. In National Institute on Drug Abuse approved studies on a secure research unit, six subjects smoked placebo, 10, 20, and 40 mg cocaine with a precise dose delivery device and six different subjects smoked 42 mg cocaine in a glass pipe. Urine specimens (n = 700) were collected for up to seven days and analyzed for cocaine (COC), benzoylecgonine (BE), ecgonine methylester (EME), m-hydroxybenzoylecgonine (mOHBE), p-hydroxybenzoylecgonine (pOHBE), norbenzoylecgonine (NBE), and ecgonine (EC) by gas chromatography-mass spectrometry. Results (mean +/- SE) for the 40-mg precise delivery doses are as follows: (Table can not be represented) Mean C(max) for all analytes linearly increased with increasing dose. T(max) was not dose-dependent. All metabolites were detected in some subjects within 2 h. EC concentrations were significantly higher after smoked cocaine in a precise delivery coil compared to a glass "crack" pipe.

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The relationship between blood cocaine concentrations and pharmacological effects is of both theoretical and practical interest. This study utilized a computer-assisted smoking device for the delivery of three active doses (10, 20, and 40 mg) of cocaine base to seven human volunteers. Doses were administered in an ascending dose design with random placement of placebo. Physiological, subjective, and performance measures were collected concurrently with blood samples. Mean peak plasma cocaine concentrations were achieved at 2 min after the 20-mg and 40-mg doses and at 5 min after the 10-mg dose. Maximal responses in systolic and diastolic blood pressure, "feel", "good" drug, and drug "liking" subjective effects were also achieved immediately after drug administration. Pupil diameter and heart rate increases demonstrated a modest counter-clockwise hysteresis in relation to plasma cocaine concentrations shortly after dosing. Systolic and diastolic blood pressure, heart rate, and some subjective and performance measures of drug effect demonstrated a biphasic response after smoked cocaine. Initial increases above baseline levels were followed by an apparent compensatory decrease below baseline levels at a later time after smoked cocaine. Despite evidence of hysteresis and biphasic responses for some measures, linear correlation was obtained between mean plasma cocaine concentrations and several pharmacological effects over a period of 4 h after dosing. Several subjective and cardiovascular measures returned to baseline levels in the presence of detectable concentrations of cocaine.

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Cocaine is transformed into hepatotoxic metabolites through oxidative pathways. For anhydroecgonine methyl ester (AEME), the main constituent in crack smoke, the oxidative metabolism has not been studied. Therefore, incubation of AEME with rat liver microsomes was performed and a metabolite of AEME, anhydroecgonine methyl ester N-oxide (AEMENO), was identified. The chemical structure of this new metabolite was confirmed by synthesis and by comparative interpretation of electrospray multiple-stage mass spectra, which were obtained in the positive ion mode. This metabolite was also detected in whole blood, serum and urine samples from crack users. The application of liquid chromatography/electrospray mass spectrometry or nanoelectrospray mass spectrometry was necessary because AEMENO is susceptible to thermal degradation during gas chromatographic/mass spectrometric analysis. This study demonstrated that AEMENO is produced by rat hepatic microsomal metabolism in vitro and is present in body fluids from crack users.

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A fim de contribuir para o entendimento da exposiçäo humana à cocaína associada ao etanol, responsáveis tanto pelos efeitos nocivos como pelos prazerosos, esta monografia trata dos padröes de uso cocaína e seus produtos, sua disposiçäo cinética, bem como da formaçäo do produto de transesterificaçäo, com etanol: o cocaetileno. Dados relativos aos parâmetros toxicocinéticos säo descritos e discutidos.

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OBJECTIVE: To review and discuss the differences and similarities between the use of crack cocaine and cocaine hydrochloride; and to determine how these findings might affect policies on the imprisonment and treatment of cocaine users. DATA SOURCES: English-language publications were identified through a computerized search (using MEDLINE) between 1976 and 1996 using the search terms "smoked cocaine," "crack cocaine," "freebase," and "cocaine-base." In addition, manual searches were conducted on references cited in original research articles, reviews, and an annotated bibliography, and on selected journals. STUDY SELECTION: Only those articles that compared various routes of cocaine administration or types of cocaine (cocaine base or crack cocaine vs cocaine hydrochloride) were examined. DATA EXTRACTION: Studies were reviewed to obtain information on the composition of the 2 forms of cocaine, and the prevalence, pharmacokinetics and pharmacodynamics, abuse liability, pattern of use, and consequences across the various routes of cocaine administration and forms of cocaine. CONCLUSION: Cocaine hydrochloride is readily converted to base prior to use. The physiological and psychoactive effects of cocaine are similar regardless of whether it is in the form of cocaine hydrochloride or crack cocaine (cocaine base). However, evidence exists showing a greater abuse liability, greater propensity for dependence, and more severe consequences when cocaine is smoked (cocaine-base) or injected intravenously (cocaine hydrochloride) compared with intranasal use (cocaine hydrochloride). The crucial variables appear to be the immediacy, duration, and magnitude of cocaine's effect, as well as the frequency and amount of cocaine used rather than the form of the cocaine. Furthermore, cocaine hydrochloride used intranasally may be a gateway drug or behavior to using crack cocaine. Based on these findings, the federal sentencing guidelines allowing possession of 100 times more cocaine hydrochloride than crack cocaine to trigger mandatory minimum penalties is deemed excessive. Although crack cocaine has been linked with crime to a greater extent than cocaine hydrochloride, many of these crimes are associated with the addiction to cocaine. Therefore, those addicted individuals who are incarcerated for the sale or possession of cocaine are better served by treatment than prison.

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Cocaine hepatotoxicity in mice has been reported by numerous investigators. Such hepatotoxicity in other animal models has been more difficult to produce. We prospectively assessed 1212 alcoholics admitted for detoxification for historical, clinical and laboratory evidence of concomitant cocaine/crack use and evidence of liver disease. The 470 cocaine positive subjects had both longer durations and higher average daily costs of cocaine/crack use than the 742 cocaine negative subjects, but had a shorter duration of alcohol use. Serum transaminases were higher in the cocaine negative group. There were no clinically severe cases of liver disease or rhabdomyolysis in either group. Serum hepatitis B surface antibody and hepatitis A antibody were more frequent in the cocaine positive subjects. In conclusion, in this large sample of alcoholics abusing cocaine, severe hepatotoxicity was not at all evident. The previous reports of hepatotoxicity may represent co-morbidity. Some possibilities include infection with a hepatitis or other virus, the presence of an adulterant, an idiosyncratic reaction or an enzymatic abnormality.

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