This four-way, unblinded, uncontrolled comparison by University of Michigan pharmacist H.J. Zhu and colleagues (from the University of South Carolina, Medical University of South Carolina, and the University of Tennessee) (H.J. Zhu and colleagues, Journal of Clinical Psycho- pharmacology 37(4): 419-428, 2017) regretably suffers from a lack of blindedness and placebo control that its torturously long discussion leaves unassuaged.
The authors administered d-methylphenidate (Focalin, 20 milligrams) or d,l-methylphenidate (Ritalin, 40 milligrams) to a small sample (eight men, six women), of whom each received each methylphenidate formulation with or without a single dose of ethanol (0.6 mg/kg), administered four hours later. They then assayed plasma concentrations of each over the next eight hours and administered a visual analog rating scale intended to detect and quantitate subjective experience of stimulation and “feeling high.”
Peak plasma concentrations (Cmax) were higher after their subjects consumed alcohol than when they did not, with mean increases of 35 percent for d,l-methylphenidate and 27 percent for d-methylphenidate. (Absolute baseline and peak plasma concentrations, both before and after alcohol consumption were similar for d- and d,l-methylphenidate. Mean partial bioavailability (area under the time-plasma drug concentration curve) was slightly higher during the four hours after alcohol consumption (statistically significant only for d,l-methylphenidate) than during the same four-hour interval on occasions when no alcohol was administered. Subjective visual-analog self-ratings detected feelings of stimulation and “feeling high” during the same four-hour intervals after d-methylphenidate and d,l-methylphenidate, as well as during the subsequent four-hour interval after alcohol consumption (was similar for the two methylphenidate formulations). No clinically significant adverse effects were attributable to alcohol dosing four hours after dosing with d-methylphenidate or d,l-methylphenidate.
Acknowledging the methodologic compromises of their finding, the authors believe tyhat methylphenidate bioavailability may increase after alcohol consumption. They are unsure whether the increment may devolve from an effect on methylphenidate clearance; more likely, they believe, may be enhancement by alcohol of methylphenidate absorption after oral consumption. (Obiter: Evidence so far fails to indicate clinically significant pharmacokinetic or pharmacodynamic interactivity between any formulation of methylphenidate and alcohol in healthy, non-elderly persons.)