Zhu_2017_J.Clin.Psychopharmacol_37_419

Reference

Title : Ethanol Interactions With Dexmethylphenidate and dl-Methylphenidate Spheroidal Oral Drug Absorption Systems in Healthy Volunteers - Zhu_2017_J.Clin.Psychopharmacol_37_419
Author(s) : Zhu HJ , Patrick KS , Straughn AB , Reeves OT, 3rd , Bernstein H , Shi J , Johnson HJ , Knight JM , Smith AT , Malcolm RJ , Markowitz JS
Ref : J Clin Psychopharmacol , 37 :419 , 2017
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.
ESTHER : Zhu_2017_J.Clin.Psychopharmacol_37_419
PubMedSearch : Zhu_2017_J.Clin.Psychopharmacol_37_419
PubMedID: 28590363

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Citations formats

Zhu HJ, Patrick KS, Straughn AB, Reeves OT, 3rd, Bernstein H, Shi J, Johnson HJ, Knight JM, Smith AT, Malcolm RJ, Markowitz JS (2017)
Ethanol Interactions With Dexmethylphenidate and dl-Methylphenidate Spheroidal Oral Drug Absorption Systems in Healthy Volunteers
J Clin Psychopharmacol 37 :419

Zhu HJ, Patrick KS, Straughn AB, Reeves OT, 3rd, Bernstein H, Shi J, Johnson HJ, Knight JM, Smith AT, Malcolm RJ, Markowitz JS (2017)
J Clin Psychopharmacol 37 :419