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Concurrent Pharmacokinetic Analysis of Plasma Cocaine and Adrenocorticotropic Hormone in Men¹

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 plasma cocaine and ACTH pharmacokinetics. Twelve healthy male occasional cocaine users participated in a double blind study. Intravenous cocaine (0.2 mg/kg) or placebo was infused over 1 min, and samples for cocaine, ACTH and cortisol analysis were collected at 2, 4, 8, 12, 16, 20, 30, 40, 60, 80, 120, 180, and 240 min. Peak cocaine plasma levels averaged 101.2 ± 14.6 ng/mL. ACTH increases were significantly correlated (P < 0.0001) with increases in plasma cocaine levels (r = 0.67; r² = 0.44). Pharmacokinetic analysis showed that the t_max (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 was calculated using the trapezoidal rule. The area under the curve for 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 ± 4.0 min, and that for ACTH was 35.8 ± 5.1 min. Cardiovascular and subjective effect measures were correlated with concurrent increases in plasma cocaine and ACTH levels.

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