Article date: February 2010
By: Linghui Li, Tom Everhart, Peyton Jacob III, Reese Jones, John Mendelson, in Volume 69, Issue 2, pages 187-192
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
AIM
To characterize the formation and urinary elimination of metabolites of S‐(+) and R‐(−) methamphetamine (MA) in humans.
METHODS
In this 12‐subject, six‐session, double‐blind, placebo‐controlled, balanced, crossover design study, the formation of the MA metabolites para hydroxymethamphetamine (pOH‐MA) and amphetamine (AMP) were determined in urine after intravenous doses of S‐(+)‐MA 0.25 and 0.5 mg kg−1, R‐(−)‐MA 0.25 and 0.5 mg kg−1, racemic MA 0.5 mg kg−1, or placebo. Parent drug and metabolite levels in urine and plasma were measured by gas chromatography‐mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental models using WinNonlin.
RESULTS
An approximately threefold enantioselectivity difference in elimination was observed for AMP, with 7% of the dose converted to S‐(+)‐AMP vs. 2% to R‐(−)‐AMP (P < 0.001). Furthermore, less R‐(−)‐pOH‐MA was excreted in the urine compared with S‐(+)‐pOH‐MA (8% vs. 11%, P= 0.02). Correspondingly, S‐(+)‐MA excretion was less than R‐(−)‐MA (42% vs. 52%; P= 0.005).
CONCLUSIONS
The metabolism of MA is enantioselective, with formation of AMP having the highest isomer selectivity. A greater percentage of MA is converted to pOH‐MA (8–11%) than AMP (2–7%). The formation of pOH‐MA was less affected by the MA enantiomer administered, suggesting that urine pOH‐MA may be a more stable biomarker of MA metabolism.
DOI: 10.1111/j.1365-2125.2009.03576.x
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