Studies on distribution and metabolism of para-methoxymethamphetamine (PMMA) in rats after subcutaneous administration

p-Methoxymethamphetamine (PMMA) is an illegal psychedelic drug of abuse derived from an amphetamine structure with a risk to health and reports of several cases of intoxications and fatalities caused by its ingestion. However, its pharmacokinetics based on a controlled study is unknown and only partial information on its biotransformation in animal models is available. Our experimental design aimed to study the disposition and kinetic profile of PMMA and its metabolites in rat plasma and selected tissues after the bolus subcutaneous dose of 40 mg/kg, using a GC–MS method. Prior to this, we performed a qualitative verification of its metabolites appearing in excreted urine fractions. PMMA maximum plasma concentration of 4014 ± 1122 ng/mL was reached 30 min after dosing, whereas the appearance of metabolites was rather delayed. The disposition of PMMA was characterized by its approximate half-life of 1.0 h, volume of distribution of 6.4 L/kg and plasma clearance of 4.4 L/h. PMMA tissue concentration exceeded plasma and the highest one was found in the lungs (cmax 42,988 ± 10,223 ng/g). Penetration through the blood/brain barrier was more efficient considering PMMA and its N-desmethylated metabolite PMA (para-methoxyamphetamine) than hydroxylated metabolites. The maximum brain/plasma ratio value of PMMA (15.8) and PMA (11.8) was reached after 8 h of observation. The experimental results ascertained could be useful for subsequent evaluation of the psychotropic or neurotoxic effects of PMMA and for diagnostic concern of intoxication.