SOFT - TIAFT 1998 Poster Session 1 Wednesday October 7, 1998

Eric T. Moolchan, Abraham T. Wtsadik, Jonathan M. Oyler, Edward J. Cone, and Robert E. Joseph, Jr.

Addiction Research Center, IRP, NIDA, NIH, Baltimore, MD, USA

An inpatient clinical study was designed to characterize the pharmacokinetics and pharmacodynamics of cocaine, codeine, and methamphetamine in human subjects. This report describes the pharmacological effects and disposition of cocaine in plasma and saliva following subcutaneous (SQ) drug administrations. Three subjects received low doses (75 mg/70 kg) and high doses (150 mg/70 kg) of cocaine hydrochloride (HCl). Pharmacological effect data (pupil diameter, heart rate, blood pressure, subject-reported "High") and blood and saliva specimens were collected simultaneously. Stimulated saliva was obtained by placing candy containing citric acid in subjects' mouths. Saliva was then collected in tubes. Biological specimens were analyzed by GC-MS for cocaine and metabolites.

Cocaine was detected in both saliva and plasma within 5-10 min following dosing, and cocaine concentrations in both matrices peaked within 30-60 min. Cmax measures for cocaine following low doses ranged from 749-1,682 ng/mL in saliva and from 258-370 ng/mL in plasma. Cocaine Cmax measures following high doses ranged from 2,342-7,249 ng/mL in saliva and from 406-655 ng/mL in plasma. Saliva/plasma cocaine ratios were generally greater than 2 in specimens collected for up to 24 hr following dosing. Benzoylecgonine (BZE) and ecgonine methyl ester (EME) were the primary cocaine metabolites detected in saliva and plasma. EME saliva/plasma ratios were generally greater than 1, and BZE saliva/plasma ratios were typically less than 1. Cocaine and metabolites were detected in plasma and saliva for approximately 24 hr following dosing.

Pharmacological effects observed after cocaine administration included increases in heart rate, elevations in blood pressure, dilation of pupils, and increases in subject-reported "High". The duration of pharmacological effects was consistently shorter than, or similar to the time course for detection of cocaine in saliva and plasma. These findings suggest that saliva testing may provide valuable insights into the onset and duration of cocaine-induced pharmacological effects. Overall, saliva testing appears to be a useful alternative to plasma testing for cocaine.

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