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.
RCT Entities:
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.
Authors: L Y Lin; E W Di Stefano; D A Schmitz; L Hsu; S W Ellis; M S Lennard; G T Tucker; A K Cho Journal: Drug Metab Dispos Date: 1997-09 Impact factor: 3.922
Authors: C E Cook; A R Jeffcoat; J M Hill; D E Pugh; P K Patetta; B M Sadler; W R White; M Perez-Reyes Journal: Drug Metab Dispos Date: 1993 Jul-Aug Impact factor: 3.922
Authors: C E Cook; A R Jeffcoat; B M Sadler; J M Hill; R D Voyksner; D E Pugh; W R White; M Perez-Reyes Journal: Drug Metab Dispos Date: 1992 Nov-Dec Impact factor: 3.922
Authors: Matthew N Newmeyer; Marta Concheiro; Jose Luiz da Costa; Ronald Flegel; David A Gorelick; Marilyn A Huestis Journal: Drug Test Anal Date: 2015-03-18 Impact factor: 3.345
Authors: Bing Wang; Samantha M Powell; Ye Guan; Nan Xu; Leonard M Thomas; George B Richter-Addo Journal: Nitric Oxide Date: 2017-04-24 Impact factor: 4.427
Authors: Stephen J Kohut; David S Jacobs; Richard B Rothman; John S Partilla; Jack Bergman; Bruce E Blough Journal: Psychopharmacology (Berl) Date: 2017-09-09 Impact factor: 4.530