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Metabolomics of Methylphenidate and Ethylphenidate: Implications in Pharmacological and Toxicological Effects

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Abstract

Methylphenidate (MPH) is primarily indicated for attention-deficit hyperactivity disorder and narcolepsy therapy. A marked individual variability in the dose–response has been observed, and therefore dosage must be titrated for optimal therapeutic effect with minimal toxicity. This variability has been claimed to be predominantly pharmacokinetic. Moreover, due to its similar pharmacodynamics to amphetamine, MPH has been abused and fatalities have been reported. This review aims to discuss metabolomics of MPH, namely by presenting all major and minor metabolites. Ritalinic acid is the main metabolite. In addition, minor pathways involving aromatic hydroxylation, microsomal oxidation and conjugation have also been reported to form the p-hydroxy-, oxo- and conjugated metabolites, respectively. MPH may undergo transesterification with ethanol producing ethylphenidate, which is also pharmacologically active. It is expected that knowing the metabolomics of MPH may provide further insights regarding individual contribution for MPH pharmacodynamics and toxicological effects, namely if ethanol is co-consumed.

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Acknowledgments

Ricardo Dinis-Oliveira acknowledges Fundação para a Ciência e a Tecnologia (FCT) for his Investigator Grant (IF/01147/2013). This work was supported by FEDER under Program PT2020 (project 007265-UID/QUI/50006/2013).

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Authors and Affiliations

  1. Department of Sciences, IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, University Institute of Health Sciences (IUCS), CESPU, CRL, Rua Central de Gandra, 1317, 4585-116, Gandra, Portugal

    Ricardo Jorge Dinis-Oliveira

  2. Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, UCIBIO-REQUIMTE, University of Porto, Porto, Portugal

    Ricardo Jorge Dinis-Oliveira

  3. Department of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto, Portugal

    Ricardo Jorge Dinis-Oliveira

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Dinis-Oliveira, R.J. Metabolomics of Methylphenidate and Ethylphenidate: Implications in Pharmacological and Toxicological Effects. Eur J Drug Metab Pharmacokinet 42, 11–16 (2017). https://doi.org/10.1007/s13318-016-0362-1

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