The percentages of DHMA conjugates to total DHMA and HMMA conjugates to total HMMA were calculated at each time point and were consistent among the 10 participants.
Urinary ratios of DHMA 3-sulfate/DHMA 4-sulfate were calculated at each time point.
Several studies have been performed to determine urinary excretion kinetics following controlled MDMA administration; in all, however, DHMA, HMMA, or HMA pharmacokinetic data were obtained after conjugate cleavage by either acid or enzymatic hydrolysis with Helix pomatia (22-25).
In this study, however, concentrations of free drugs were <5% of total DHMA and HMMA, which further indicates a sufficient stability of the phase II metabolites.
All metabolites of MDMA--namely DHMA, HMMA, DHA, and HMA--were detected as glucuronide and sulfate conjugates.
Although the median [C.sub.max] of MDMA was significantly higher (P = 0.002) after high-dose MDMA, no significant differences in [C.sub.max] values were observed after low and high doses for DHMA 3-sulfate, DHMA 4-sulfate, HMMA sulfate, and HMMA glucuronide.
The significantly lower HMMA sulfate and glucuronide percentages, combined with no significant differences in DHMA and DHMA sulfate percentages, might indicate inhibition of catecol-O-methyltransferase by DHMA, also demonstrated in vitro (31).
Sulfation of the 3,4-methylenedioxymethamphetamine (MDMA) metabolites 3,4-dihydroxymethamphetamine (DHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA) and their capability to inhibit human sulfotransferases.