Abstract
The relationship between xenobiotic concentrations in hair and the degree of systemic xenobiotic exposure is poorly defined. The purpose of this study was to evaluate the effect of dose, time, and pigment on the hair incorporation of cocaine (COC) and its metabolites, benzoylecgonine (BE), ecgonine methyl ester (EME), and norcocaine (NCOC). COC was administered by the i.p. route to male Long-Evans (LE) rats at three doses (5, 10, and 20 mg/kg) once daily for 5 days. Fourteen days after the initial injection, the hair was collected and analyzed by gas chromatography/mass spectrometry for the compounds of interest. COC, EME, and NCOC were preferentially incorporated into pigmented hair in a dose-dependent manner. None of the analytes were detected in nonpigmented hair. The plasma pharmacokinetic profile of each analyte was determined at each dose. After normalizing for the plasma concentrations, the incorporation of COC into pigmented hair was 2 orders of magnitude greater than BE. The time course of COC and metabolite distribution into hair was also investigated from 1 h to 14 days after a single dose. After COC disappears from plasma, there is a 3-day delay before maximal hair concentrations are reached in pigmented hair. In nonpigmented hair, concentrations of BE and COC did not exceed 0.25 ng/mg and were undetectable after 4 h and 2 days, respectively. This study demonstrates that the pigment-mediated differences in the incorporation of COC and its metabolites noted at 14 days after dosing are also evident a few hours after drug administration.
Footnotes
-
Send reprint requests to: Dr. Douglas E. Rollins, Center for Human Toxicology, University of Utah, 20 S. 2030 E., Rm. 490, Salt Lake City, UT 84112-9457. E-mail: drollins{at}alanine.pharm.utah.edu
-
This research supported by National Institute on Drug Abuse (NIDA) Grant DA-078280.
- Abbreviations used are::
- PCP
- phencyclidine
- COC
- cocaine
- BE
- bezoylecgonine
- EME
- ecgonine methyl ester
- NCOC
- norcocaine
- SPE
- solid phase extraction
- ICR
- incorporation ratio
- LLOD
- lower limit of detection
- LLOQ
- lower limit of quantitation
- LE
- Long-Evans
- GC/MS
- gas chromatography/mass spectrometry
- Received June 12, 2000.
- Accepted August 23, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|