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Transdermal dl‐methylphenidate potentiates the pharmacokinetic interaction with ethanol relative to oral dosing in a mouse model
Author(s) -
Bell Guinevere Hannah,
Novak Andrew,
Griffin William,
Patrick Kennerly
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb531
Subject(s) - transdermal , pharmacology , pharmacokinetics , dosing , active metabolite , ethanol , oral administration , medicine , chemistry , biochemistry
Objective Test the hypothesis that transdermal dl‐methylphenidate (MPH) potentiates the pharmacokinetic interaction with ethanol relative to oral MPH dosing; thus resulting in a greater elevation of d‐MPH and the metabolite l‐ethylphenidate (EPH) in blood, brain and urine. Methods A novel murine model of transdermal MPH was developed using ¼ of a 12.5cm 2 MPH patch (Daytrana ® ) with/without ethanol (3 g/kg po). Used MPH patches were analyzed to determine the average dose delivered (7.5 mg/kg) and this dose was used for oral MPH‐ethanol comparisons. MPH and EPH were enantioselectively quantified by GC‐MS of prolyl derivatized piperidyl fragments. Results The concentration of d‐MPH was significantly elevated by ethanol, especially following transdermal dosing. Approximately 10X more l‐MPH reached the blood with transdermal delivery vs. oral. In the ethanol‐transdermal MPH group, the concentration of l‐EPH was significantly higher than d‐EPH. Conclusions The greater ethanol‐induced elevation of the “active” d‐MPH isomer when using transdermal vs. oral dosing appears to be mediated by the higher circulating levels of l‐MPH which competitively inhibit carboxylesterase 1. These findings have implications for abuse liability and cardiovascular toxicity of concomitant transdermal MPH and ethanol should this animal model hold for ADHD patients who consume ethanol. Supported by RO1AA16707.