Cocaine concentrations

S. M. Roberts, D. L. Phillips, I. R. Tebbett, Increased Blood and Brain Cocaine Concentrations with Ethanol Cotreatment in Mice , Drug Metab. Dispos. 1995, 23, 664-666. 

As shown in Table 2, cocaine concentrations are detected in almost all the studies targeting psychoactive substances or drugs of abuse in the literature, with the exception of Algiers and Serbia, where cannabinoids were found whilst cocaine was not (Tables 3 and 4). In the literature, cannabinoid concentrations are either expressed as A -tetrahydrocannbinol (THC) or as the sum of cannabinol, cannabidiol and THC (known as CBs). 

Increase cocaine concentration from 0 to 10 pM and separate the reaction mixtures as described in Subheading 3.9. 

Perez-Reyes et al.8 estimated that only 32% of a dose of cocaine base placed in a pipe is actually inhaled by the smoker. Cone9 compared the pharmacokinetics and pharmacodynamics of cocaine by the intravenous, intranasal, and smoked routes of administration in the same subjects. Venous plasma cocaine concentrations peaked within 5 min by the intravenous and smoked routes. Estimated peak cocaine concentrations ranged from 98 to 349 ng/ml and 154 to 345 ng/ml after intravenous administration of 25-mg cocaine hydrochloride and 42-mg cocaine base by the smoked route, respectively. After dosing by the intranasal route (32 mg cocaine hydrochloride) estimated peak plasma cocaine concentrations ranged from 40 to 88 ng/ml after 0.39 to 0.85 h.9 In this study, the average bioavailability of cocaine was 70.1% by the smoked route and 93.7% by the intranasal route. Jenkins et al.10 described the correlation between pharmacological effects and plasma cocaine concentrations in seven volunteers after they had smoked 10 to 40 mg cocaine. The mean plasma... 

The disposition of cocaine in nontraditional testing matrices has been described. For example, Lester et al.15 measured cocaine and benzoylecgonine (BE) concentrations in skin, interstitial fluid (IF), sebum, and stratum corneum in five volunteers after the intravenous 1-h infusion of 1 mg/kg cocaine d5. Peak cocaine concentrations in the skin were achieved at 1.5 h and were undetectable after 6 h. No BE was measured in the skin. Peak cocaine concentrations were achieved at 5 h after administration in the IF and were non detectable by 24 h. BE was found in the IF. In the sebum peak cocaine concentrations occurred between 3 to 24 h but in the stratum corneum cocaine was detected in only one subject. 

Jenkins, A.J., Keenan, R.M., Henningfield, J.E., and Cone, E.J., Correlation between pharmacological effects and plasma cocaine concentrations after smoked administration, J. Anal. Toxicol., 26, 382-392, 2002. 

The cardiac effects of intracoronary infusion of cocaine have been studied in dogs and humans (42). The procedure can be performed safely and does not alter coronary arterial blood flow. The effects of direct intracoronary infusion of cocaine on left ventricle systolic and diastolic performance have been studied in 20 patients referred for cardiac catheterization for evaluation of chest pain. They were given saline or cocaine hydrochloride (1 mg/minute) in 15-minute intracoronary infusions, and cardiac measurements were made during the final 2-3 minutes of each infusion. The blood cocaine concentration obtained from the coronary sinus was 3.0 pg/ml, which is similar in magnitude to the blood-cocaine concentration reported in abusers who die of cocaine intoxication. Minimal systemic effects were produced. The overall results were that cocaine caused measurable deterioration of left ventricular systolic and diastolic performance. 

The criteria for the interpretation of cocaine concentrations in biological samples and their relation to the cause of death has been comprehensively reviewed (234). The importance of scene investigation, forensic autopsy, and forensic sampling for drug analysis has been discussed, with particular emphasis on the need to use appropriate blood preservatives and interpretation of the half-life and concentrations of cocaine and its metabolites, benzylec-gonine and ethylcocaine, in combined cocaine + alcohol abuse. 

There have been two studies of the neurodevelopmen-tal effects of cocaine during the first 48 hours of life. In the first, 23 cocaine-exposed and 29 non-exposed infants were prospectively assessed within the first 48 hours of life infant meconium was used to detect cocaine and the BNBA Scale was used for clinical assessment (278). One-third of the cocaine-exposed neonates were bom to women who denied cocaine use. In six of the seven clusters assessed, cocaine-exposed infants fared badly compared with control infants. The cocaine-exposed infants had poor autonomic stability and there was a dose-response relation between meconium cocaine concentration and poor performance in relation to orientation and so-called regulation of state, which refers to how the infant responds when aroused. The authors concluded that cocaine exposure is independently related to poor behavioral performance in areas that are central to optimal infant development. They emphasized the value of the identification and quantification of cocaine in infants. 

The uptake of cocaine to hair after preliminary exposure to various acidic and basic solutions is shown in Figure 10. Three sets of experiments were performed. In the first experiment, hair was exposed to base (0.1 M sodium carbonate, pH 12) for 3 h and then washed extensively with water rmtil the water was neutral. This was then followed by two phosphate buffer rinses at pH 5.3 for 10-min periods. The hair was then exposed to 5 pg/mL of cocaine, containing a radioactive tracer, in phosphate buffer at pH 5.3 for 1 h. After exposure the excess cocaine was removed with three water rinses of 10 min each and the hair was dried. Then the hair was decontaminated with ethanol and six phosphate washes, digested, and the cocaine concentration determined by scintillation counting as per previously described procedures. Approximately twice as much cocaine was incorporated into the hair pretreated by exposure to base as compared to hair not subjected to any pretreatment. In the second experiment, hair was pretreated with 0.1 M HCl, then treated as in the first experiment. In this case approximately one sixth as much cocaine was incorporated as the control. In the third experiment, hair was pretreated with 5% acetic add and treated as in the... 

Cocaine Concentrations (ng/mg) in Hair of the Head, Axillary, and Pubic Regions... 

Benzoylecgonine concentrations in both arm and head hair were lower than cocaine concentrations in all cases. Heroin was detected in only two head hair samples, while 6-acetylmorphine was detected in extracts of 14 hair samples and in 6 arm hair samples. If present, 6-acetylmorphine concentrations also tended to be higher in arm hair than in head hair with no significant difference. Morphine was detected only in extracts of 3 head hair samples at a concentration lower than the respective 6-acetylmorphine one. 

Cocaine" concentration (mgml ) Cocaine peak area (arbitrary units) Internal standard peak area (arbitrary units) Y-value" XxY... 

Next, the peak areas of the drugs in the standards are obtained, and the relative responses calculated. Some exemplar standard data for the quantification of cocaine in a drng sample are presented in Table 6.3. Using these, a calibration graph of relative response against cocaine concentration, as the free base, is plotted (Figure 6.3), and from the simultaneous equations ... 

The physiological levels of cocaine can reach a maximum of about 0.3 micromolar (M) in serum immediately after cocaine administration (Jeffcoat et al. 1989). These levels are much less than the Km of the liver benzoyl esterase (0.7 mM). Hence, the enzyme will obey first-order kinetics, where activity equals k at/KM, called the catalytic efficiency, times the cocaine concentration. The catal5Tic efficiency of the liver benzoyl esterase, 11 min mM", is similar to human serum cholinesterase, 7 min mM ", another enzyme that catalyzes the hydrolysis of the benzoyl group of cocaine. The content and kinetic properties of serum cholinesterase and liver benzoyl esterase need to be evaluated to determine which enz5mie has the greater capacity for hydrolysis of cocaine in human. 

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