Absorption and clearance of +/-3,4-methylenedioxymethamphetamine from the plasma of neonatal rats

A limited number of studies exist describing the effects of +/-3,4-methylenedioxymethamphetamine (MDMA) during perinatal development, although the number of MDMA users has increased dramatically, and this increase is greatest in people of child-bearing age. Previous experimental studies show that exposure to MDMA during part of the third trimester-equivalent (postnatal days P1-20 in rats) cause two distinct types of learning and memory deficits (sequential and spatial) if exposed on P11-20, but not if exposure occurs on P1-10. In the present study, we examined differences in the ability of neonatal rats to eliminate MDMA. Rat offspring were given a single dose of 20 mg/kg MDMA on either P1 or 11, and plasma was collected at 1 of 10 time points during a 10-h period. MDMA concentrations were assessed by liquid chromatography/mass spectrometry (LC/MS). Indices of absorption did not differ as a function of exposure age. Exposure age differences in the clearance rate and half-life of MDMA were observed, such that the P1-treated animals had a significantly more rapid clearance and a shorter half-life than P11-treated animals did. These changes are in the same direction as the behavioral differences reported previously between P1-10 and P11-20 MDMA exposure groups. However, the pharmacokinetic differences were not commensurate with the behavioral changes in that the clearance differences at the two ages are quantitative whereas the behavioral differences were qualitative (no effects from P1-10 exposure and large effects from P11-20). Although the data do not suggest a mechanism for the learning deficits, they indicate that pharmacokinetic differences may contribute to the effects seen when exposure is begun on P11.