title: Comparative Ethanol-Induced Potentiation of Stimulatory Responses to Dexmethylphenidate Versus Methylphenidate.
abstract: The potentiation of positive subjective responses to immediate-release dexmethylphenidate (d-MPH) or dl-methylphenidate (dl-MPH) by ethanol was investigated over the time course of maximal drug exposure after a single dose. In a 4-way, randomized, crossover study design, 12 men and 12 women normal volunteers received d-MPH (0.15 mg/kg) or dl-MPH (0.3 mg/kg) with or without ethanol (0.6 g/kg). Serial visual analog scales were used as surrogates for drug abuse liability ("high," "good," "like," "stimulated," and "any drug effect"). Combining pure d-MPH with ethanol significantly (P < 0.005) increased the area under the effect curves (AUC(0-5.25h)) of all 5 subscales. The dl-MPH-ethanol combination significantly (P < 0.05) increased these AUCs with the exception of like (P = 0.08). Effects of the pure d-MPH-ethanol combination exhibited delayed potentiation relative to dl-MPH-ethanol. A pharmacokinetic interaction between the l-isomer of dl-MPH and ethanol has previously been shown to increase early exposure to d-MPH. Administration of the pure isomer d-MPH precludes this absorption phase pharmacokinetic interaction with ethanol. This notwithstanding, the pure d-MPH-ethanol combination resulted in comparable, if not greater, cumulative stimulant potentiation than the dl-MPH-ethanol combination. These findings provide evidence of a pharmacodynamic component to d-MPH-ethanol synergistic interactions and carry implications for the rational drug individualization in the treatment of attention-deficit/hyperactivity disorder.
authors.affiliation: From the *Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC; †Department of Pharmaceutical Sciences, University of Tennessee Health Sciences Center, Memphis, TN; and ‡Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC.
authors.forename: Kennerly S
authors.initials: KS
authors.lastname: Patrick
authors.forename: Arthur B
authors.initials: AB
authors.lastname: Straughn
authors.forename: Owen T
authors.initials: OT
authors.lastname: Reeves
authors.forename: Hilary
authors.initials: H
authors.lastname: Bernstein
authors.forename: Robert
authors.initials: R
authors.lastname: Malcolm
mesh_terms: D000339:Affect / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D018592:Cross-Over Studies; D064699:Dexmethylphenidate Hydrochloride / Q000008:administration & dosage*; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*
chemical_list: D000697:Central Nervous System Stimulants; D064699:Dexmethylphenidate Hydrochloride; D008774:Methylphenidate; D000431:Ethanol