Methamphetamine blood concentrations in human abusers: Application to pharmacokinetic modeling

Characterization of methamphetamine's (METH) dose‐dependent effects on brain neurochemistry may represent a critical component for better understanding the range of resultant behavioral pathologies. Most human studies, however, have assessed only the effects of long term, high dose METH abuse (...

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Bibliographic Details
Published in:Synapse (New York, N.Y.) N.Y.), 2007-04, Vol.61 (4), p.216-220
Main Authors: Melega, William P., Cho, Arthur K., Harvey, Dennis, Laćan, Goran
Format: Article
Language:English
Subjects:
amphetamine
Amphetamine - blood
Amphetamine - pharmacokinetics
Central Nervous System Stimulants - blood
Central Nervous System Stimulants - pharmacokinetics
Dose-Response Relationship, Drug
drug abuse
Forensic Medicine
Humans
Methamphetamine - blood
Methamphetamine - pharmacokinetics
Substance-Related Disorders - blood
Time Factors
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Summary:Characterization of methamphetamine's (METH) dose‐dependent effects on brain neurochemistry may represent a critical component for better understanding the range of resultant behavioral pathologies. Most human studies, however, have assessed only the effects of long term, high dose METH abuse (e.g., greater than 1000 mg/day) in individuals meeting DSM‐IV criteria for METH dependence. Yet, for the majority of METH abusers, their patterns of METH exposure that consist of lower doses remain less well‐characterized. In this study, blood samples were obtained from 105 individuals detained by police for possible criminal activity and testing positive for stimulants by EMIT assay. METH blood concentrations were subsequently quantified by GC‐MS and were predominantly in the low micromolar range (0.1–11.1 μM), with median and mean values of 1.3 μM (0.19 mg/l) and 2 μM (0.3 mg/l), respectively. Pharmacokinetic calculations based on these measured values were used to estimate initial METH body burdens, the median value being 52 mg. Modeling a 52 mg dose for a 4 day–METH maintenance exposure pattern of 4 doses/day at 4 h intervals showed that blood concentrations remained between 1 and 4 μM during this period. Collectively, these data present evidence for a METH exposure pattern distinct from high dose‐METH abuse and provide the rationale for assessing potential brain pathology associated with such lower dose‐METH exposure. Synapse 61:216–220, 2007. © 2007 Wiley‐Liss, Inc.
ISSN:0887-4476
1098-2396
DOI:10.1002/syn.20365