Addiction Pharmacology Research Laboratory, California Pacific Medical Center Research Institute, San Francisco, CA 94110, USA.
Br J Clin Pharmacol. 2010 Feb;69(2):187-92. doi: 10.1111/j.1365-2125.2009.03576.x.
To characterize the formation and urinary elimination of metabolites of S-(+) and R-(-) methamphetamine (MA) in humans.
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.
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).
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.
描述 S-(+)和 R-(-)甲基苯丙胺（MA）在人体内的代谢物形成和尿液排泄情况。
在这项包含 12 名受试者的、6 个周期的、双盲、安慰剂对照、均衡、交叉设计研究中，静脉注射 S-(+)-MA 0.25 和 0.5 mg/kg、R-(-)-MA 0.25 和 0.5 mg/kg、外消旋 MA 0.5 mg/kg 或安慰剂后，通过气相色谱-质谱法测定 MA 代谢物对羟甲基苯丙胺（pOH-MA）和苯丙胺（AMP）在尿液中的形成情况。尿液和血浆中的母体药物和代谢物水平通过非房室模型计算，采用 WinNonlin 软件。
AMP 的消除存在约 3 倍的对映选择性差异，7%的剂量转化为 S-(+)-AMP，而 2%转化为 R-(-)-AMP（P<0.001）。此外，与 S-(+)-pOH-MA 相比，R-(-)-pOH-MA 在尿液中的排泄量较少（8%比 11%，P=0.02）。相应地，S-(+)-MA 的排泄量少于 R-(-)-MA（42%比 52%；P=0.005）。
MA 的代谢具有对映选择性，AMP 的形成具有最高的异构体选择性。与 AMP（2-7%）相比，pOH-MA（8-11%）的形成量更大。pOH-MA 的形成受给予的 MA 对映体影响较小，这表明尿液中 pOH-MA 可能是 MA 代谢的更稳定的生物标志物。
