Transdermal and oral dl ‐methylphenidate – ethanol interactions in C57BL/6J mice: Locomotor activity and brain d‐ , l‐ methylphenidate

The interaction of dl‐ methylphenidate (MPH) and ethanol (EtOH) results in an elevation of the active d ‐MPH plasma concentration and enantioselective transesterification to yield the biomarker l‐ ethylphenidate (EPH). The present study reports on a C57BL/6J mouse model of dl‐ MPH induced locomotor activity which was potentiated by an otherwise sedating dose of oral EtOH (3 g/kg). Concomitant oral dl ‐MPH (7.5 mg/kg) and EtOH significantly increased the locomotor activity induced by oral dl‐ MPH alone over a 100 min period. Transdermal dl ‐MPH (¼ of a 12.5 cm 2 patch; mean dose 7.5 mg/kg) induced locomotor activity only after a lag phase of 60 min and this effect was not potentiated by EtOH. Using chiral derivatization and GC‐MS, mean 3 h brain concentrations of d ‐MPH found to be significantly elevated by EtOH in both the oral (65% increase) and transdermal (88% increase) groups. The corresponding l‐ EPH brain concentrations were 10 ng/g and 130 ng/g for the oral and transdermal groups, respectively. Clinical implications of these findings will be presented in the context of increased abuse potential and side effect liability for this drug combination.