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Ethanol Interactions With Dexmethylphenidate and dl-Methylphenidate Spheroidal Oral Drug Absorption Systems in Healthy Volunteers. | LitMetric

Ethanol Interactions With Dexmethylphenidate and dl-Methylphenidate Spheroidal Oral Drug Absorption Systems in Healthy Volunteers.

J Clin Psychopharmacol

From the *Department of Clinical Pharmacy, University of Michigan, Ann Arbor, MI; †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; §Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC; and ∥Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, FL.

Published: August 2017

AI Article Synopsis

  • * A study with 14 subjects showed that ethanol impacts the metabolism and absorption of MPH rather than its formulation in the stomach.
  • * The results suggest that understanding how ethanol interacts with MPH could help in choosing effective treatments for individuals dealing with both ADHD and alcohol use disorder.

Article Abstract

Background/purpose: Ethanol coadministered with immediate-release dl-methylphenidate (dl-MPH) or dexmethylphenidate (d-MPH) significantly increases the geomean maximum plasma concentration (Cmax) of d-MPH 22% and 15%, respectively, and elevates overall drug exposure and psychostimulant effects. We asked the question: Are these ethanol-MPH interactions based more fundamentally on (1) inhibition of postabsorption d-MPH metabolism or (2) acceleration of MPH formulation gastric dissolution by ethanol in the stomach? This was investigated using the pulsatile, distinctly biphasic, spheroidal oral drug absorption systems of dl-MPH and d-MPH.

Methods: In a randomized, 4-way crossover study, 14 healthy subjects received pulsatile dl-MPH (40 mg) or d-MPH (20 mg), with or without ethanol (0.6 g/kg), dosed 4 hours later. These 4 hours allowed the delayed-release second MPH pulse to reach a more distal region of the gut to preclude gastric biopharmaceutical influences. Plasma was analyzed using a highly sensitive chiral method. Subjective/physiological effects were recorded.

Findings/results: Ethanol increased the second pulse of d-MPH Cmax for dl-MPH by 35% (P < 0.01) and the partial area under the plasma concentration curve from 4 to 8 hours by 25% (P < 0.05). The respective values for enantiopure d-MPH were 27% (P = 0.001) and 20% (P < 0.01). The carboxylesterase 1-mediated transesterification metabolite ethylphenidate served as a biomarker for coexposure. Ethanol significantly potentiated stimulant responses to either formulation.

Implications/conclusions: These findings support drug dispositional interactions between ethanol and MPH as dominant over potential biopharmaceutical considerations. Understanding the pharmacology underlying the frequent coabuse of MPH-ethanol provides rational guidance in the selection of first-line pharmacotherapy for comorbid attention-deficit/hyperactivity disorder-alcohol use disorder.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484776PMC
http://dx.doi.org/10.1097/JCP.0000000000000721DOI Listing

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