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).
Joseph
R E
RE
Addiction Research Center, Division of Intramural Research, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA.
Oyler
J M
JM
Wstadik
A T
AT
Ohuoha
C
C
Cone
E J
EJ
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D044383:Black People; D003042:Cocaine / Q000032:analysis / Q000494:pharmacology*; D003061:Codeine / Q000032:analysis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004817:Epidermis / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007279:Injections, Subcutaneous; D007297:Inpatients; D008297:Male; D009294:Narcotics / Q000032:analysis / Q000494:pharmacology*; D010147:Pain Measurement; D011597:Psychomotor Performance / Q000187:drug effects; D011680:Pupil / Q000187:drug effects; D012629:Sebum / Q000737:chemistry*; D019966:Substance-Related Disorders / Q000378:metabolism; D014018:Tissue Distribution; D001741:Black or African American
D009294:Narcotics; D003042:Cocaine; D003061:Codeine