Stereoselective pharmacokinetics of 3,4‐methylenedioxymethamphetamine in the rat
Chirality – January 01, 1990
Source: OpenAlex
Summary
MDMA's pharmacokinetics reveal significant differences between its enantiomers. In a study with rats, the average half-life was 2.5 hours for (−)‐(R)‐MDMA and 2.2 hours for (+)‐(S)‐MDMA. Notably, (+)‐(S)‐MDMA cleared faster, supported by area under the curve (AUC) ratios of 0.70 for MDMA and 3.1 for its metabolite MDA. After a 20 mg/kg intravenous dose, excretion rates showed that 20% of (−)‐(R)‐MDMA and 12% of (+)‐(S)‐MDMA were eliminated, highlighting distinct metabolic pathways in forensic toxicology.
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.