Cocaine and metabolite elimination patterns in chronic cocaine users during cessation: plasma and saliva analysis.

Several reports suggest a prolonged elimination of cocaine and metabolites after chronic use compared with single or occasional use. This study was designed to measure the half-lives of cocaine in plasma and saliva of individuals who consumed cocaine on a frequent basis. The disposition and elimination patterns of cocaine and metabolites in the body fluids of chronic high-dose cocaine users during acute cessation of use were investigated. Plasma and saliva specimens were collected over a 12-h period during cessation and analyzed by gas chromatography-mass spectrometry. Pharmacokinetic parameters were derived by noncompartmental analysis of plasma and saliva data. Results indicated a cocaine terminal T(1/2) of 3.8 h in plasma and 7.9 h in saliva. The terminal T(1/2) of benzoylecgonine was 6.6 h in plasma and 9.2 h in saliva. Compared with prior studies of acute low-dose cocaine administration, these findings suggest that cocaine's half-life is longer in active street users than in occasional users though the half-life of its main metabolite benzoylecgonine remains similar (as do cocaine saliva-to-plasma ratios). Thus, regular use of cocaine appears to alter the disposition and elimination of cocaine when compared to single or occasional use.

Elimination of cocaine and metabolites in plasma, saliva, and urine following repeated oral administration to human volunteers.

Chronic administration of lipophilic drugs can result in accumulation and prolonged elimination during abstinence. It has been suggested that cocaine and/or metabolites can be detected in saliva and urine for an extended period following long-term, high-dose administration. The effects of chronic oral cocaine administration in healthy volunteer subjects with a history of cocaine abuse were investigated. Subjects were housed on a closed clinical ward and were administered oral cocaine in up to 16 daily sessions. In each session, volunteers received five equal doses of oral cocaine with 1 h between doses. Across sessions, cocaine was administered in ascending doses from an initial dose of 100 mg (500 mg/day) up to 400 mg (2 g/day), increasing by 25 mg/dose/session (125 mg/session). Participation in the study was terminated if cardiovascular safety parameters were exceeded. Plasma and saliva specimens were collected periodically during the dosing sessions and during the one-week withdrawal phase at the end of the study. All urine specimens were collected throughout the entire study. Specimens were analyzed for cocaine and metabolites by solid-phase extraction followed by gas chromatographic-mass spectrometric analysis in the SIM mode. The limit of detection for each analyte was approximately 1 ng/mL. The analytes measured included benzoylecgonine (BZE), ecgonine methyl ester, cocaine, benzoylnorecgonine, norcocaine, m- and p-hydroxycocaine, and m- and p-hydroxybenzoylecgonine. Noncompartmental analysis was employed for the determination of plasma and saliva pharmacokinetic parameters. Urinary elimination half-lives for cocaine and metabolites were determined by constructing ARE (amount remaining to be excreted) plots. Two phases of urinary elimination of cocaine and metabolites were observed. An initial elimination phase was observed during withdrawal that was similar to the elimination pattern observed after acute dosing. The mean (N = 6) plasma, saliva, and urine cocaine elimination half-lives were 1.5 +/- 0.1 h, 1.2 +/- 0.2 h, and 4.1 +/- 0.9 h, respectively. For three subjects, the mean cocaine urinary elimination half-life for the terminal phase was 19.0 +/- 4.2 h. There was some difficulty in determining if a terminal elimination phase for cocaine was present for the remaining three subjects because of interference by high concentrations of BZE. A terminal elimination phase was also observed for cocaine metabolites with half-life estimates ranging from 14.6 to 52.4 h. These terminal elimination half-lives greatly exceeded previous estimates from studies of acute cocaine administration. These data suggest that cocaine accumulates in the body with chronic use resulting in a prolonged terminal elimination phase for cocaine and metabolites.

Sweat testing for cocaine, codeine and metabolites by gas chromatography-mass spectrometry.

Sweat testing for drugs of abuse provides a convenient and considerably less invasive method for monitoring drug exposure than blood or urine. Numerous devices have been developed for collection of sweat specimens. The most common device in current use is the PharmChek Sweat Patch, which usually is worn by an individual for five to ten days. This device has been utilized in several field trials comparing sweat test results to conventional urinalysis and the results have been favorable. Two new Fast Patch devices have been developed and tested that allow rapid collection of sweat specimens. The Hand-held Fast Patch was applied to the palm of the hand and the Torso Fast Patch was applied to the abdomen or the sides of the trunk (flanks) of volunteer subjects participating in a research study. Both patches employed heat-induced sweat stimulation and a larger cellulose pad for increased drug collection. Sweat specimens were collected for 30 min at various times following administration of cocaine or codeine in controlled dosing studies. After patch removal, the cellulose pad was extracted with sodium acetate buffer, followed by solid-phase extraction. Extracts were derivatized and analyzed by gas chromatography mass spectrometry (GC-MS) simultaneously for cocaine, codeine and metabolites. Cocaine and codeine were the primary analytes detected in sweat. Peak cocaine and codeine concentrations ranged from 33 to 3579 ng/patch and 11 to 1123 ng/patch, respectively, across all doses for the Hand-held Patch compared to 22-1463 ng/patch and 12-360 ng/patch, respectively, for the Torso Fast Patch. Peak concentrations generally occurred 4.5-24 h after dosing. Both drugs could be detected for at least 48 h after dosing. Considerably smaller concentrations of metabolites of cocaine and codeine were also present in some patches. Generally, concentrations of cocaine and codeine were higher in sweat specimens collected with the Hand-held Fast Patch than for the Torso Fast Patch. Drug concentrations were also considerably higher than those reported for the PharmChek Sweat Patch. The predominance of cocaine and codeine in sweat over metabolites is consistent with earlier studies of cocaine and codeine secretion in sweat. Multiple mechanisms appear to be operative in determining the amount of drug and metabolite secreted in sweat including passive diffusion from blood into sweat glands and outward transdermal migration of the drug. Additional important factors are the physico-chemical properties of the drug analyte, specific characteristics of the sweat collection device, site of sweat collection and, in this study, the application of heat to increase the amount of drug secreted.

Drug testing with alternative matrices I. Pharmacological effects and disposition of cocaine and codeine in plasma, sebum, and stratum corneum.

This study examined the disposition of cocaine, codeine, and metabolites in stratum corneum, sebum, and plasma collected from five African-American males after administrations of cocaine and codeine during a 10-week inpatient clinical study. The subjects were experienced, healthy drug users with a recent history of cocaine and heroin abuse. The first drug administration was delayed by three weeks to allow for the elimination of previously administered drugs from the body. Subjects received three 75 mg cocaine hydrochloride/70 kg doses by the subcutaneous route and three 60 mg codeine sulfate/70 kg doses by the oral route on alternating days beginning in week 4. The same dosing sequence was repeated in week 8 with doubled (x 2) doses. Pharmacological measures (heart rate, pupil diameter, subject "High" and "Liking") were obtained simultaneously with blood. Stratum corneum was collected by scraping regions of the back once each week. Sebum was collected periodically from the forehead by applying Sebutape patches for 1-2-h intervals. Plasma, stratum corneum, and sebum were analyzed for cocaine, codeine, and metabolites by gas chromatography-mass spectrometry. Peak plasma cocaine concentrations occurred within the 30 min following dosing and followed peak pharmacological effects. Peak plasma codeine concentrations occurred within 1-2 h of dosing and before peak pharmacological effects. Cocaine and codeine were the primary analytes in sebum and stratum corneum. After dosing, these drugs appeared in sebum within 1-2 h and were detected for 1-2 days. Peak-drug concentrations in stratum corneum occurred one day after completion of dosing; elimination of the drugs continued over the next 1-2 weeks after dosing. Overall, no definitive relationship was observed between drug concentrations in sebum and stratum corneum compared with dose. Interpretation of drug distribution and elimination in sebum and stratum corneum was complicated by possible contamination of specimens with drugs from sweat. The mechanism(s) for deposition of cocaine and codeine in sebum and stratum corneum appeared to be complex and could involve the transfer of drugs between different body fluids (i.e., sebum and sweat) and other matrices (i.e., skin and hair).