Stereoselective pharmacokinetics of 3,4‐methylenedioxymethamphetamine in the rat

The pharmacokinetics of MDMA enantiomers were studied in rats using iliac arterial cannulation. Intravenous and subcutaneous routes were tested at two dose levels each. The average half-life for (−)-(R)-MDMA was 2.5 ± 0.8 hours and for (+)-(S)-MDMA was 2.2 ± 0.8 hours. (+)-(S)-MDMA was cleared more rapidly than (−)-(R)-MDMA, consistent with area under the curve data for the parent drug and its primary metabolite MDA. The mean AUC S/R ratios for MDMA and MDA were 0.70 ± 0.05 and 3.1 ± 0.8, respectively. After a 20 mg/kg intravenous dose, the percent dose excreted as (−)-(R)-MDMA, (+)-(S)-MDMA, (−)-(R)-MDA, and (+)-(S)-MDA were 20 ± 10, 12 ± 6, 3 ± 1, and 6 ± 2, respectively.

Study at a glance

Abstract

Abstract Studies to characterize the pharmacokinetics of the enantiomers of MDMA were conducted in rats using the iliac arterial cannulation. Two routes of administration, intravenous and subcutaneous, were evaluated at two dose levels for each route [20 and 40 mg/kg (±)‐MDMA for subcutaneous, 10 and 20 mg/kg (±)‐MDMA for intravenous administrations]. The average half‐life (±SD) for all dosing groups was 2.5 ± 0.8 h for (−)‐(R)‐MDMA and 2.2 ±0.8 h for (+)‐(S)‐MDMA. The more rapid clearnace of (+)‐(S)‐MDMA compared with (−)‐(R)‐MDMA is consistent with the area under the curve (AUC) data of the parent drug and its primary metabolite MDA. The mean (±SD) AUC S/R ratios of MDMA and MDA were 0.70 ± 0.05 and 3.1 ± 0.8, respectively. Following a 20 mg/kg dose of racemic MDMA iv the mean (±SD) of the percent dose excreted as (−)‐(R)‐MDMA, (+)‐(S)‐MDMA, (−)‐(R)‐MDA, and (+)‐(S)‐MDA were 20 ± 10, 12 ± 6, 3 ± 1, and 6 ± 2, respectively.