Concurrent Pharmacokinetic Analysis of Plasma Cocaine and Adrenocorticotropic Hormone in Men1
Michelle B. Sholar,
Jack H. Mendelson,
Nancy K. Mello,
Arthur J. Siegel,
Marc J. Kaufman,
Jonathan M. Levin,
Perry F. Renshaw and
Bruce M. Cohen
McLean Hospital/Harvard Medical School, Alcohol and Drug Abuse
Research Center, McLean Hospital, Belmont, Massachusetts 02178
Address all correspondence and requests for reprints to: Jack H. Mendelson, M.D., Alcohol and Drug Abuse Research Center, McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02178.
The purpose of this study was to determine the covariance between
plasmacocaine and ACTH pharmacokinetics. Twelve healthy male
occasionalcocaine users participated in a double blind study.
Intravenouscocaine (0.2 mg/kg) or placebo was infused over 1 min, and
samplesfor cocaine, ACTH and cortisol analysis were collected at 2,4,
8, 12, 16, 20, 30, 40, 60, 80, 120, 180, and 240 min. Peakcocaine
plasma levels averaged 101.2 ± 14.6 ng/mL. ACTHincreases were
significantly correlated (P < 0.0001) with
increasesin plasma cocaine levels (r = 0.67; r2 =
0.44). Pharmacokineticanalysis showed that the tmax
(observed time to maximum concentration)values for cocaine (6.0
± 1.4 min) and ACTH (7.3 ±1.2 min) were almost identical. The
area under the curve wascalculated using the trapezoidal rule. The
area under the curvefor plasma cocaine was 6463 ± 1070
ng/min·mL,and the area under the curve for ACTH was 1873 ± 188
pmol/min·L.The mean half-life for plasma cocaine was 46.7 ±
4.0min, and that for ACTH was 35.8 ± 5.1 min. Cardiovascularand
subjective effect measures were correlated with concurrentincreases in
plasma cocaine and ACTH levels.
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