Comparative Ethanol-Induced Potentiation of Stimulatory Responses to Dexmethylphenidate Versus Methylphenidate. Issue 4 (August 2015)

• Record Type: Journal Article
• Authors: Patrick, Kennerly S.; Straughn, Arthur B.; Reeves, Owen T.; Bernstein, Hilary; Malcolm, Robert
• Is Part Of: Journal of clinical psychopharmacology. Volume 35:Issue 4(2015)
• Publication Date: 2015-08
• Subjects: dexmethylphenidate -- methylphenidate -- ethanol -- abuse; Psychopharmacology -- Periodicals; Psychopharmacology -- Periodicals; Psychopharmacologie -- Périodiques; Psychopharmacology; Periodicals; 615.78
• DOI: 10.1097/JCP.0000000000000348
• Languages: English
• ISSNs: 0271-0749

Abstract

Abstract : 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 (AUC0–5.25h ) 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.