Simultaneous determination of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates and interaction in the rat

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Recreational use of Ecstacy, or (±)-3, 4-methylenedioxymethamphetamine (MDMA), is often associated with other drugs, among which ethanol is one of the most common in the dance club and rave cultures. The effect of ethanol coadministartion on MDMA pharmacokinetics and body temperature was investigated in male Sprague-Dawley rats. MDMA plasma concentration-time profiles were characterized after intraperitoneal (i.p.) administration of 10 and 30 mg/kg MDMA alone and of MDMA with 1.5 g/kg ethanol to rats. Rats were sacrificed at 4 h after i.p. MDMA administration, and plasma and brain were collected. Plasma and brain samples were analyzed by gas chromatography-mass spectrometry (GC-MS). Following i.p. administration, the peak MDMA plasma concentration (C_<max>) were obtained 10-20 min after administration of both concentrations. Co-administration of ethanol with MDMA was significantly increased MDMA concentration in plasma than MDMA alone (p<0.05). Following i.p. ethanol dosing, C_<max> was about 1.6 mg/ml at 20 min, and it was not detected after 4 h. The disposition kinetics of MDMA in rats was adequately described by a two-compartment open body model. MDA and MDMA concentration in the brain were not different among the four groups after 4 h. MDA was a predominant metabolite of MDMA. It was also analyzed by GC-MS. MDMA and MDA are well distributed into the brain with ethanol. Although the temperature decreased after ethanol alone i.p. injection, it increased after MDMA i.p. injection. The enhancement of MDMA effects in the ethanol combination may be due to initially increased MDMA plasma concentration followed by the effect of MDMA in the brain, might explain the enhancement of MDMA effects in the ethanol combination condition.