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Clinical Chemistry 48: 1486-1496, 2002;
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(Clinical Chemistry. 2002;48:1486-1496.)
© 2002 American Association for Clinical Chemistry, Inc.

Plasma and Oral Fluid Pharmacokinetics and Pharmacodynamics after Oral Codeine Administration

Insook Kim1, Allan J. Barnes1, Jonathan M. Oyler1, Raf Schepers1, Robert E. Joseph, Jr2, Edward J. Cone3, Diana Lafko1, Eric T. Moolchan1 and Marilyn A. Huestis1a

1 Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, 5500 Nathan Shock Dr., Baltimore, MD 21224.

2 Clinical Affairs, Amgen Inc., 1 Amgen Center Dr., Thousand Oaks, CA 91320-1799.

3 ConeChem Research, 441 Fairtree Dr., Severna Park, MD 21146.

aAuthor for correspondence. Fax 410-550-2971; e-mail mhuestis{at}intra.nida.nih.gov.

Background: The ease, noninvasiveness, and safety of oral fluid collection have increased the use of this alternative matrix for drugs-of-abuse testing; however, few controlled drug administration data are available to aid in the interpretation of oral fluid results.

Methods: Single oral codeine doses (60 and 120 mg/70 kg) were administered to 19 volunteers. Oral fluid and plasma were analyzed for free codeine, norcodeine, morphine, and normorphine by solid-phase extraction combined with gas chromatography–mass spectrometry (SPE/GC-MS). Physiologic and subjective effects were examined.

Results: Mean (SE) peak codeine concentrations were 214.2 ± 27.6 and 474.3 ± 77.0 µg/L in plasma and 638.4 ± 64.4 and 1599.3 ± 241.0 µg/L in oral fluid. The oral fluid-to-plasma ratio for codeine was relatively constant (~4) from 1 to 12 h. The mean half-life (t1/2) of codeine was 2.2 ± 0.10 h in plasma and 2.2 ± 0.16 h in oral fluid. Significant dose-related miosis and increases in sedation, psychotomimetic effect, and "high" occurred after the high dose. Mean codeine oral fluid detection time was 21 h with a 2.5 µg/L cutoff, longer than that of plasma (12–16 h). Detection times with the proposed Substance Abuse and Mental Health Services Administration cutoff (40 µg/L) were only 7 h. Norcodeine, but not morphine or normorphine, was quantified in both plasma and oral fluid.

Conclusions: The disposition of codeine over time was similar in plasma and oral fluid, but because of high variability, oral fluid codeine concentrations did not reliably predict concurrent plasma concentrations. Oral fluid testing is a useful alternative matrix for monitoring codeine exposure with a detection window of 7–21 h for single doses, depending on cutoff concentrations. These controlled drug administration data should aid in the interpretation of oral fluid codeine results.




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M. N. Win, J. S. Klein, and C. D. Smolke
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E. W. Schwilke, A. J. Barnes, S. L. Kacinko, E. J. Cone, E. T. Moolchan, and M. A. Huestis
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H. V. Pai, R. P. Kommaddi, S. J. Chinta, T. Mori, M. R. Boyd, and V. Ravindranath
A Frameshift Mutation and Alternate Splicing in Human Brain Generate a Functional Form of the Pseudogene Cytochrome P4502D7 That Demethylates Codeine to Morphine
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I. Kim, A. J. Barnes, R. Schepers, E. T. Moolchan, L. Wilson, G. Cooper, C. Reid, C. Hand, and M. A. Huestis
Sensitivity and Specificity of the Cozart Microplate EIA Cocaine Oral Fluid at Proposed Screening and Confirmation Cutoffs
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