Pharmacokinetics of intravenous d- and l-methamphetamine in healthy volunteers

Abstract

Background/Aims Methamphetamine has a chiral structure. The aim of the present study was to assess the pharmacokinetics of methamphetamine enantiomers in humans. Methods In a randomized, double-blind, six-period crossover study, methamphetamine (0.25 mg/kg d- or l-, 0.5 mg/kg d-, l- or racemic (1:1) methamphetamine and placebo) was given intravenously to 12 healthy methamphetamine users. Results d-Methamphetamine showed 30% smaller AUC compared to l-methamphetamine after administration of the racemic form. However, AUCs were similar between d- and l-methamphetamine when given on separate occasions at both doses (0.25 and 0.5 mg/kg). AUC ratios for d-methamphetamine/l-methamphetamine were 0.910 (90% CI; 0.837–0.984) for the 0.25 mg/kg dose, 0.894 (0.821–0.967) for the 0.5 mg/kg dose, and 0.679 (0.623–0.736) for the racemic dose. AUC and Cmax at 0.5 mg/kg dose were twofold greater than those at 0.25 mg/kg dose for both enantiomers. The elimination half-lives were slightly longer for l-methamphetamine. Vd was similar for both formulations. AUC ratios for amphetamine/methamphetamine were significantly higher for the d-enantiomer (16–17%) than the l-enantiomer (3–4%). Conclusions d- and l-Methamphetamine are apparently bioequivalent in terms of AUC when given separately, with linear pharmacokinetics between 0.25 and 0.5 mg/kg doses. However, administration of d-methamphetamine results in a higher metabolite concentration compared to the l-form. NIDA DA12521 and DA12393. Clinical Pharmacology & Therapeutics (2005) 77, P37–P37; doi: 10.1016/j.clpt.2004.12.034